Carbonyl Ylides Research Articles

5-Diazo Dihydrouracils: Preparation and Some Transformations.

An approach to a new type of diazo reagents─diazo dihydrouracils─has been developed, and various transformations of the obtained diazo heterocycles have been studied, demonstrating their high synthetic potential for obtaining structurally diverse derivatives based on the privileged dihydrouracil scaffold. The X-H insertion reactions provide high yields of a variety of 5-substituted dihydrouracils. Cyclopropanation and 1,3-dipolar cycloaddition reactions involving a carbonyl ylide intermediate have been carried out to give spiro-annulated derivatives. The limitations of the modification methods with respect to the nature of substituents on the nitrogen atoms of the diazo heterocycle have been outlined.

Catalytic Epoxidation of Carbonyl Compounds via Carbonyl Ylides: from Racemic to Enantioselective.

Transition metal-catalyzed epoxidation of carbonyl compounds through carbonyl ylides represents a highly effective method for synthesizing a diverse range of valuable epoxides. This review offers an in-depth overview of the latest developments in inter- and intramolecular epoxidation reactions involving metal carbenes and carbonyl compounds, encompassing both racemic to enantioselective transformations. These catalytic epoxidations are reviewed by highlighting their product selectivity, diversity and applicability, and the related mechanistic rationale is showcased where possible.

Cooperative Rh/Achiral Phosphoric Acid-Enabled [3+3] Cycloannulation of Carbonyl Ylides with Quinone Monoimines: Synthesis of Benzofused Dioxabicyclo[3.2.1]octane Scaffolds.

A cooperative Rh/achiral phosphoric acid-enabled [3+3] cycloaddition of in situ-generated carbonyl ylides with quinone monoimines has been developed. With the ability to build up the molecular complexity rapidly and efficiently, this method furnishes highly functionalized oxa-bridged benzofused dioxabicyclo[3.2.1]octane scaffolds bearing two quaternary centers in good to excellent yields under mild conditions. Moreover, the utility of the current method was demonstrated by gram-scale synthesis and elaboration of the products into various functionalized oxa-bridged heterocycles.

Expedient (3+3)-annulation of carbonyl ylides with azaoxyallyl cations: formal access to oxa-benzo[c]azepin-3-ones.

The cascade carbon-carbon and carbon-nitrogen bond formation between in situ generated carbonyl ylides and azaoxyallyl cations, facilitated by Rh-catalysis and a base, has been achieved to furnish oxa-benzo[c]azepin-3-ones. Substrate scope, functional group diversity, scale-up and post-synthetic utilities are the important practical features.

Three-component modular synthesis of chiral 1,3-dioxoles via a Rh-catalyzed carbenic olefination cascade.

The advance of organic synthesis and the discovery of novel chemical transformations are often propelled by the rational programming of various bond-forming mechanisms and sequences that involve delicate reactive intermediates. In this study, we present an innovative Rh(ii)-catalyzed asymmetric three-component cascade reaction involving IIII/PV-hybrid ylides, aldehydes, and carboxylic acids for the synthesis of 1,3-dioxoles with moderate to good yields and high enantioselectivity. This method utilizes IIII/PV-hybrid ylides as carbene precursors to form α-PV-Rh-carbenes, which initiate the formation of carbonyl ylides, followed by stereoselective cyclization with carboxylate anions and an intramolecular Wittig olefination cascade, ultimately resulting in the modular assembly of chiral 1,3-dioxoles. By employing this strategy, we successfully coupled various aldehydes and carboxylic acids to give chiral non-benzofused 1,3-dioxole scaffolds, highlighting the potential for late-stage functionalization of biologically relevant molecules, versatile synthetic manipulation, and the production of poly-1,3-dioxole macromolecules.

Comparison of metal-carbenoid reactions of β-2-five-membered heteroaryl substituted α,β-unsaturated ketones.

In this study, β-2-heteroaryl substituted (N-methyl 2-pyrrolyl, 2-thiophenyl, 2-furyl) α,β-unsaturated ketones were reacted with two α-diazo carbonyl compounds that had different characteristics (dimethyl diazo malonate and 1-diazo-1-phenyl-propane-2-one) in the presence of both copper and rhodium catalysts. In the case of reactions with N-methyl 2-pyrrolyl α,β-unsaturated ketones, the major product was the insertion derivative. However, in the reactions of 2-thiophenyl and 2-furyl α,β-unsaturated ketones with dimethyl diazomalonate (acceptor-acceptor disubstituted), only dihydrofuran products were formed over carbonyl ylides. When 2-thiophenyl and 2-furyl α,β-unsaturated ketones were reacted with 1-diazo-1-phenyl-propane-2-one (donor-acceptor disubstituted), 1-phenylpropane-1,2-dione was obtained under our reaction conditions.

Ru-Catalyzed Intermolecular [4+3] Cycloaddition of ortho-Quinone Methides with Carbonyl Ylides

Ru-Catalyzed Intermolecular [4+3] Cycloaddition of ortho-Quinone Methides with Carbonyl Ylides

Mechanochemical Degradation of Poly(vinyl chloride) into Nontoxic Water-Soluble Products via Sequential Dechlorination, Heterolytic Oxirane Ring-Opening, and Hydrolysis.

As one of the most widely used commodity plastics, poly(vinyl chloride) (PVC) is extensively used worldwide, yet is difficult to recycle and is often discarded immediately after use. Its end-of-life treatment often generates toxic hydrogen chloride and dioxins that pose a critical threat to ecosystems. To address this challenge, the mechanochemical degradation of PVC into water-soluble biocompatible products is presented herein. Oxirane mechanophores are strategically introduced into the polymeric backbone via sequential dechlorination followed by epoxidation. The oxirane mechanophore in the polymer backbone undergoes a force-induced heterolytic ring-opening to carbonyl ylide intermediates, which eventually generates acetals during the course of the reaction. The subsequent hydrolysis of the backbone acetals affords the scission of the polymeric chain into water-soluble low-molecular-weight fragments. Combined with its low cytotoxicity and phytotoxicity, this solvent-free mechanochemical degradation process offers a green alternative for the degradation of PVC.

Synthesis of Oxo-Bridged Dibenzoazocines through Ruthenium-Catalyzed [4 + 3]-Cycloannulation of Aza-ortho-quinone Methides with Carbonyl Ylides.

Oxo-bridged dibenzoazocines are furnished within a single synthetic step at room temperature via ruthenium-catalyzed [4 + 3]-cycloannulation of aza-ortho-quinone methides with carbonyl ylides. Exclusive diastereoselectivity, excellent yield, mild reaction conditions, and broad substrate scope are distinguishing features of this protocol. The product could be prepared on a gram scale and could be further functionalized into diverse substituted dihydroisobenzofuran derivatives and a dibenzoazocine scaffold.

Blue LED induced three component reactions for the generation of 4, 6-dioxo-hexahydro-1H-furo[3, 4-c] pyrrole: Their evaluation as anticancer agents through PARP inhibition.

Herein we report a catalyst, metal and additive free generation of carbonyl ylides by blue LED irradiation of aryl diazoacetates in presence of aldehydes. The resulting ylides underwent [3+2] cycloaddition with substituted maleimides present in the reaction mixture to afford 4, 6-dioxo-hexahydro-1H-furo[3, 4-c] pyrrole in excellent yields. Fifty compounds were synthesized based on this scaffold. Molecular docking indicated them to be potential poly ADP ribose polymerase (PARP) inhibitor. Screening a representative member of the library against PARP enzyme revealed a few potential inhibitors with IC50 of 600-700 nM. The phenotypic screening against MCF7, A549 and HePG2 cells furthermore indicated that these compounds selectively inhibit the proliferation of A549, HeLa and HePG2 cells with IC50 of 1 - 2 mM. The mechanism of action of the most active compound at the cellular level was investigated.

Ir(I)-Catalyzed Synthesis of Furanones from Vinyl Sulfoxonium Ylides.

A method for the synthesis of allyl substituted γ-butenolides via carbonyl ylide rearrangement of vinyl sulfoxonium ylide-derived carbenes has been developed. At rt, the mechanism involves a carbonyl ylide generation/allyloxy furan formation/[3,3]-sigmatropic rearrangement/isomerization sequence for the generation of 3-allyl butenolides. At 70 °C, instead of the final isomerization step, the resulting [3,3]-sigmatropic rearrangement product undergoes further [3,3]-sigmatropic rearrangement to produce 5-allyl butenolide. In the absence of the catalyst, the reaction affords a diene via [2,3]-sigmatropic rearrangement.

Copper-catalyzed reactions of β-alkoxy/phenoxy enones with dimethyl diazomalonate.

2,3-dihydrofurans were synthesized from carbonyl-ylides via 1,5-electrocyclization reactions with high yields. Dimethyl diazomalonate was reacted with several β-alkoxy and/or β-phenoxy α,β-unsaturated compounds in the presence of Cu(acac)2 as a catalyst. From the reaction of β-methoxy enone with diazo compound, dioxole, and Cα-H insertion products were also obtained as side products along with 2,3-dihydrofuran derivative. When the unsaturated compound has an ester and a ketone group, only one dihydrofuran derivative was formed, which occurred by the 1,5-ring closure of keto-carbonyl ylide. Dihydrofuran derivative from the formation of ester carbonyl ylide in the reactions was not obtained.

Rapid assembly of stereochemically rich polycyclic tetrahydrofurans by a conjugate addition-Rh(II) catalysis sequence

An efficient reaction sequence that gives stereochemically rich, polycyclic tetrahydrofurans is described. A highly diastereoselective conjugate addition of enoxy silanes to vinyl diazonium salts gives 2-diazo-1,5‑dicarbonyl compounds in yields up to 99%. The diazo functional group can then be taken advantage of in subsequent Rh catalyzed carbonyl ylide 1,3-dipolar cycloaddition or OH insertion reactions to give tetrahydrofuran products that contain up to 6 contiguous stereocenters in yields up to 89%.

Enantioselective Copper-Catalyzed Formal [2+1] and [4+1] Annulations of Diynes with Ketones via Carbonyl Ylides.

Carbonyl ylides have proven to be powerful synthons for the efficient construction of various valuable O-heterocycles, and the formation of carbonyl ylides by the reaction of metal carbenes with carbonyls has attracted increasing attention over the past decades. However, a catalyst-controlled highly enantioselective reaction of carbonyl ylides from metal carbenes is extremely challenging. Herein, we report a novel copper-catalyzed asymmetric formal [2+1] and [4+1] annulations of diynes with ketones via carbonyl ylides. Importantly, this protocol not only represents the first example of successful asymmetric epoxidation via carbonyl ylides, but also constitutes the first reaction of vinyl cations with carbonyl compounds. This method leads to the divergent, practical and atom-economical synthesis of a range of chiral oxiranes and dihydrofurans in moderate to excellent yields with generally excellent enantioselectivities and diastereoselectivities via remote-stereocontrol strategy.

Enantioselective Copper‐Catalyzed Formal [2+1] and [4+1] Annulations of Diynes with Ketones via Carbonyl Ylides

AbstractCarbonyl ylides have proven to be powerful synthons for the efficient construction of various valuable O‐heterocycles, and the formation of carbonyl ylides by the reaction of metal carbenes with carbonyls has attracted increasing attention over the past decades. However, a catalyst‐controlled highly enantioselective reaction of carbonyl ylides from metal carbenes is extremely challenging. Herein, we report a novel copper‐catalyzed asymmetric formal [2+1] and [4+1] annulations of diynes with ketones via carbonyl ylides. Importantly, this protocol not only represents the first example of successful asymmetric epoxidation via carbonyl ylides, but also constitutes the first reaction of vinyl cations with carbonyl compounds. This method leads to the divergent, practical and atom‐economical synthesis of a range of chiral oxiranes and dihydrofurans in moderate to excellent yields with generally excellent enantioselectivities and diastereoselectivities via remote‐stereocontrol strategy.

Rhodium‐Catalyzed Transannulation of N‐Sulfonyl‐1,2,3‐triazoles with Carboxylic Esters

AbstractA rhodium‐catalyzed transannulation of N‐sulfonyl‐1,2,3‐triazoles with carboxylic esters followed by acid‐mediated aromatization has been developed, affording a variety of 2,5‐disubstituted oxazole derivatives in good to high yields under mild reaction conditions. The present transformation is proposed to involve the intermolecular carbonyl ylide formation between in situ generated α‐imino rhodium carbene species and carboxylic esters, which undergoes the nucleophilic attack of the neighboring α‐imino moiety.magnified image

Asymmetric Cycloadditions of Acyclic Carbonyl Ylides with Aldehydes Catalyzed by a Chiral Binaphthyldiimine-Ni(II) Complex: Enantioselective Synthesis of 1,3-Dioxolanes and Mechanistic Studies by DFT Calculations.

Chiral binaphthyldiimine-Ni(II)-catalyzed asymmetric 1,3-dipolar cycloaddition reactions between acyclic carbonyl ylides generated from donor-acceptor oxiranes and aldehydes are reported. Both aromatic and aliphatic aldehydes could be used as dipolarophiles, providing cis-1,3-dioxolanes with high diastereo- and enantioselectivities. On the basis of mechanistic studies, a monomeric chiral Ni(II) complex was hypothesized to act as the active species for the cycloaddition. The high levels of asymmetric induction are satisfactorily explained by a concerted-asynchronous endo Si-face approach of the aldehyde.

Construction of Oxo-Bridged Diazocines via Rhodium-Catalyzed (4+3) Cycloaddition of Carbonyl Ylides with Azoalkenes.

Developing efficient strategies for synthesizing novel diazocine compounds is valuable because their use has been limited by their synthetic accessibility. This work describes the catalytic (4+3) cycloaddition reaction of carbonyl ylides with azoalkenes generated in situ. The rhodium-catalyzed cascade reaction features good atom and step economy, providing the first access to oxo-bridged diazocines. The product could be synthesized on a gram scale and converted into diversely substituted dihydroisobenzofurans.

A theoretical study on the proton affinity of sulfur ylides

The proton affinities of sulfoxide ylides, carbonyl ylides, allyl ylides, benzenyl ylides and heterocyclic ylides with typical substituents were investigated using the SOGGA11-X functional.

Concise stereoselective and stereodivergent syntheses of (±)-melicolones A and B

The first total syntheses of the epimeric (±)-melicolones A and B, which are bioactive constituents isolated as racemates from the leaves of Melicope ptelefolia, were achieved in 12.3% combined overall yield. The divergent approach to these unusual natural products is remarkably concise and required a longest linear sequence of only nine steps (11 total steps) from commercially available starting materials. The significant synthetic challenge posed by the unique and densely functionalized polycyclic framework characteristic of the melicolones was addressed by a novel and highly regioselective (16:1) and diastereoselective (15:1) dipolar cycloaddition to deliver the oxabicycloheptane core. This pivotal reaction featured an innovative combination of an unsaturated vinylogous ester dipolarophile with a carbonyl ylide that was generated by an unusual cyclization of the carbonyl oxygen atom of an aliphatic aldehyde with a rhodium carbenoid. Stereoselective prenylation of the ketone enolate derived from this bicyclic core gave an intermediate that was processed via a one-pot O-demethylation cycloaldolization sequence to give the penultimate intermediate. The synthesis was completed by a bioinspired tandem epoxidation of the prenyl substituent followed by a regioselective, acid-catalyzed cyclization to deliver (±)-melicolones A and B. This approach may be applicable to the syntheses of other melicolones having a tetracyclic core.