Protocol Features Mild Reaction Conditions Research Articles

Photochemical oxidation of alcohols to ketones or aldehydes using DMSO as an oxidant without activated agent

We report visible light mediated oxidation of alcohols to ketones or aldehydes catalyzed by anthraquinone under irradiation at 430–440 nm at room temperature, using DMSO as an oxidant without activated agent. Key parameters, including irradiating wave-length, reaction medium and photocatalyst, are investigated. According this procedure, a variety of alcohols are oxidized to the corresponding ketones or aldehydes in satisfactory yields. This protocol features transition metal free and mild reaction conditions.

Sequential 1,3-Dipole Cycloaddition of Nitrile Imines with Alkenyl Isoxazoles and Aromatization: A One-Pot Access to 1,3,4-Triarylpyrazoles

AbstractA novel one-pot two-step process for the preparation of 1,3,4-triarylpyrazoles is disclosed. This process involves a 1,3-dipolar cycloaddition reaction of alkenyl isoxazoles with nitrile imines generated in situ, followed by SnCl2-promoted aromatization/elimination reaction to give a range of 1,3,4-triarylpyrazoles in a fully regioselective manner. This protocol features mild reaction conditions, easily available raw materials, and excellent regioselectivity.

I2/FeCl3-Catalyzed Domino Reaction of Aurones with Enamino Esters for the Synthesis of Highly Functionalized Pyrroles.

A novel and efficient I2/FeCl3-catalyzed domino reaction of aurones with enamino esters via Michael addition, iodination, intramolecular nucleophilic substitution, and spiro ring opening processes has been developed, affording a vast variety of polysubstituted pyrroles in moderate to excellent yields. This protocol features mild reaction conditions, broad substrate scope, high atom economy and efficiency, and feasibility for large-scale synthesis. A plausible mechanism for the pyrrole synthesis is proposed.

Excited-State Copper-Catalyzed [4 + 1] Annulation Reaction Enables Modular Synthesis of α,β-Unsaturated-γ-Lactams.

Synthesis of α,β-unsaturated-γ-lactams continue to attract attention due to the importance of this structural motif in organic chemistry. Herein, we report the development of a visible-light-induced excited-state copper-catalyzed [4 + 1] annulation reaction for the preparation of a wide range of γ-H, -OH, and -OR-substituted α,β-unsaturated-γ-lactams using acrylamides as the 4-atom unit and aroyl chlorides as the 1-atom unit. This modular synthetic protocol features mild reaction conditions, broad substrate scope, and high functional group tolerance. The reaction is amenable to late-stage diversification of complex molecular architectures, including derivatives of marketed drugs. The products of the reaction can serve as versatile building blocks for further derivatization. Preliminary mechanistic studies suggest an inner-sphere catalytic cycle involving photoexcitation of the Cu(BINAP) catalyst, single-electron transfer, and capture of radical intermediates by copper species, followed by reductive elimination or protonation to give the desired γ-functionalized α,β-unsaturated-γ-lactams.

Ag@TiO2 Nanocomposite as an Efficient Catalyst for Knoevenagel Condensation.

In the present study, a new series of different heterocycles was synthesized through base-free Knoevenagel condensation of various aldehydes and active methylene-containing compounds using the hydrothermal developed Ag@TiO2 as a heterogeneous catalyst. The catalyst was synthesized by mixing TiO2 (P25) with AgNO3 and hydrothermally treated in ethanol at 180 °C for 12 h. The developed Ag@TiO2 catalyst was directly applied for Knoevenagel condensation, and the optimized procedure involved stirring the aldehydes and active methylene-containing compounds with Ag@TiO2 in ethanol at 65 °C. The reaction scope was investigated for various aromatic and heterocyclic aldehydes with active methylene-containing compounds, and the isolated yields were significantly high. The reusability of the catalyst was investigated for up to five cycles, where an insignificant decrease in the catalyst’s reactivity was observed. Also, the reaction could proceed in water as a solvent, and the isolated yield was 40%. Hence, this protocol features mild reaction conditions, a facile procedure, and clean reaction profiles.

Facile access to β-hydroxyl ketones via a cobalt-catalyzed ring-opening/hydroxylation cascade of cyclopropanols

A cobalt-catalyzed ring-opening/hydroxylation cascade of highly strained cyclopropanols has been developed for the first time. The reaction was conducted under open-air atmosphere to afford a broad series of structurally diverse β-hydroxy ketones in moderate to good yields with high regioselectivity. The protocol features mild reaction conditions, simple operation, high-functional-group tolerance, facile scalability, and heterocycle compatibility.

Solvent-Free Mechanosynthesis of Polysubstituted 1,2-Dihydroquinolines from Anilines and Alkyne Esters.

A novel one-pot reaction of anilines with acetylenedicarboxylate diesters in the presence of boron trifluoride, iodine, and trifluoroacetic acid or methylsulfonic acid has been developed under solvent-free ball-milling conditions, affording a variety of polysubstituted 1,2-dihydroquinolines bearing multiple ester groups in moderate to excellent yields. The present protocol features mild reaction conditions, short reaction time, and feasibility of large-scale synthesis, providing a facile and practical alternative to 1,2-dihydroquinoline synthesis. Intriguingly, the generated 1,2-dihydroquinolines can be further transformed into quinoline derivatives.

Enantioselective Cobalt-Catalyzed Hydroboration of Ketone-Derived Silyl Enol Ethers.

Catalytic asymmetric hydroboration of alkenes is a powerful tool for the synthesis of natural products, agrochemicals, and pharmaceuticals via the versatile transformations of chiral alkyl boronic esters. However, the scope of available alkenes is limited to styrenes, activated alkenes, and compounds with directing groups. The catalytic enantioselective hydroboration of heteroatom-substituted alkenes is rarely explored and those catalyzed by earth-abundant metals are yet to be reported. Herein, we report a cobalt-catalyzed asymmetric hydroboration of ketone-derived silyl enol ethers and provide a convenient approach to access valuable enantiopure β-hydroxy boronic esters. This protocol features mild reaction conditions, a broad substrate scope, and excellent enantioselectivities (up to 99 % ee). This approach was applied in the successful synthesis of salmeterol and albuterol, demonstrating its potential to streamline complex molecule synthesis.

Enantioselective Cobalt‐Catalyzed Hydroboration of Ketone‐Derived Silyl Enol Ethers

Catalytic asymmetric hydroboration of alkenes is a powerful tool for the synthesis of natural products, agrochemicals, and pharmaceuticals via the versatile transformations of chiral alkyl boronic esters. However, the scope of available alkenes is limited to styrenes, activated alkenes, and compounds with directing groups. The catalytic enantioselective hydroboration of heteroatom-substituted alkenes is rarely explored and those catalyzed by earth-abundant metals are yet to be reported. Herein, we report a cobalt-catalyzed asymmetric hydroboration of ketone-derived silyl enol ethers and provide a convenient approach to access valuable enantiopure β-hydroxy boronic esters. This protocol features mild reaction conditions, a broad substrate scope, and excellent enantioselectivities (up to 99 % ee). This approach was applied in the successful synthesis of salmeterol and albuterol, demonstrating its potential to streamline complex molecule synthesis.

Efficient Synthesis of Dihydropyrimidines Using a Highly Ordered Mesoporous Functionalized Pyridinium Organosilica

A Brönsted acidic ionic solid pyridinium-functionalized organosilica network (PMO-Py-IL) was demonstrated to efficiently catalyse one-pot Biginelli condensation reaction. The green synthesis of 3,4-dihydro-2(H)-pyrimidinones (DHPMs) with high yield was carried out via one-pot three component condensation of β- dicarbonyls, aldehydes, and urea in the presence of a catalytic amount of PMO-Py-IL nanomaterial as an efficient nanocatalyst under solvent free conditions. Furthermore, the catalyst showed outstanding stability and could be easily separated and reused for at least ten reaction runs without significant loss of activity and product selectivity. The green protocol features simple set-up, cost-effectiveness, easy work-up, eco-friendly and mild reaction conditions.

Copper-Catalyzed Divergent C-H Functionalization Reaction of Quinoxalin-2(1H)-ones and Alkynes Controlled by N1-Substituents for the Synthesis of (Z)-Enaminones and Furo[2,3-b]quinoxalines.

With control by N1-substituents, the switchable divergent C-H functionalization reaction of quinoxalin-2(1H)-ones is achieved for the synthesis of (Z)-enaminones and furo[2,3-b]quinoxalines using the combination of a copper catalyst and an oxidant. This new protocol features mild reaction conditions, readily available materials, and a broad substrate scope. Gram-scale and mechanistic studies were also investigated. Furthermore, the desired products exhibited excellent antitumor activity against A549, HepG-2, MCF-7, and HeLa cells, which were tested by MTT assay.

Redox-neutral C–H acylation of indole with ketene by manganese catalysis

A low-cost manganese-catalyzed oxidant-free selective C–H acylation of indole with ketene is reported. This protocol features mild reaction conditions and good functional group tolerance. The yield is from middle to excellent. The acylation products can be further converted to diverse useful compounds. Mechanism study reveals the acylation transformation possibly undergoes a cyclomanganated complex species as reactive intermediate.

Hexafluoroisopropanol (HFIP)-prompted rearrangement of N-phenoxysulfonamides for the direct assembly of ortho-sulfonamide phenols: A combined experimental and computational study

ortho-Sulfonamide phenols represent a class of attractive structural motifs in medicinal and synthetic chemistry. Herein an efficient metal-free rearrangement reaction has been developed for the construction of ortho-sulfonamide phenols via HFIP-prompted intramolecular sulfonamide group 1,3-migration. This protocol features mild reaction conditions, broad functional group compatibility and good regioselectivity. Combined experimental mechanistic study and detailed DFT calculations clarified the crucial role of HFIP molecules in facilitating this reaction, and the unique hydrogen bond network had been deduced to account for the observed reactivity.

Cu-Catalyzed C-H Allylation of Benzimidazoles with Allenes.

CuH-catalyzed intramolecular cyclization and intermolecular allylation of benzimidazoles with allenes have been described. The reaction proceeded smoothly with the catalytic system of Cu(OAc)2/Xantphos and catalytic amount of (MeO)2MeSiH. This protocol features mild reaction conditions and a good tolerance of substrates bearing electron-withdrawing, electron-donating, or electron-neutral groups. A new catalytic mechanism was proposed for this copper hydride catalytic system.

Cascade Lactonization/Benzannulation of Propargylamines with Dimethyl 3-Oxoglutarate for Modular Assembly of Hydroxylated/Arene-Functionalized Benzo[c]chromen-6-ones

A DBU-mediated cascade strategy of propargylamines with dimethyl 3-oxoglutarate for constructing a functionalized benzo[c]chromen-6-one core has been achieved. This cascade process presumably involves a sequence of 1,4-conjugate addition, followed by lactonization, alkyne-allene isomerization, enol-keto tautomerization, 6π-electrocyclization, and aromatization. This protocol features mild reaction conditions, simple operation, rich structural diversity, and good functional group tolerance. A photophysical survey reveals that the benzo[c]chromen-6-one products exhibit fluorescence properties and show potential for exploring fluorescent material applications.

Asymmetric Alkoxy‐ and Hydroxy‐Carbonylations of Functionalized Alkenes Assisted by β‐Carbonyl Groups

AbstractAs a fundamental type of carbonylation reaction, the alkoxy‐ and hydroxy‐carbonylation of unsaturated hydrocarbons constitutes one of the most important industrial applications of homogeneous catalysis. However, owing to the difficulties in controlling multi‐selectivities for asymmetric hydrocarbonylation of alkenes, this reaction is typically limited to vinylarenes and analogues. In this work, a highly efficient asymmetric alkoxy‐ and hydroxy‐carbonylation of β‐carbonyl functionalized alkenes was developed, providing practical and easy access to various densely functionalized chiral molecules with high optical purity from broadly available alkenes, CO, and nucleophiles (>90 examples, 84–99 % ee). This protocol features mild reaction conditions and a broad substrate scope, and the products can be readily transformed into a diverse array of chiral heterocycles. Control experiments revealed the key role of the β‐carbonyl group in determining the enantioselectivity and promoting the activity, which facilitates chiral induction by coordination to the transition metal as rationalized by DFT calculations. The strategy of utilizing an innate functional group as the directing group on the alkene substrate might find further applications in catalytic asymmetric hydrocarbonylation reactions.

Asymmetric Alkoxy- and Hydroxy-Carbonylations of Functionalized Alkenes Assisted by β-Carbonyl Groups.

As a fundamental type of carbonylation reaction, the alkoxy- and hydroxy-carbonylation of unsaturated hydrocarbons constitutes one of the most important industrial applications of homogeneous catalysis. However, owing to the difficulties in controlling multi-selectivities for asymmetric hydrocarbonylation of alkenes, this reaction is typically limited to vinylarenes and analogues. In this work, a highly efficient asymmetric alkoxy- and hydroxy-carbonylation of β-carbonyl functionalized alkenes was developed, providing practical and easy access to various densely functionalized chiral molecules with high optical purity from broadly available alkenes, CO, and nucleophiles (>90 examples, 84-99 % ee). This protocol features mild reaction conditions and a broad substrate scope, and the products can be readily transformed into a diverse array of chiral heterocycles. Control experiments revealed the key role of the β-carbonyl group in determining the enantioselectivity and promoting the activity, which facilitates chiral induction by coordination to the transition metal as rationalized by DFT calculations. The strategy of utilizing an innate functional group as the directing group on the alkene substrate might find further applications in catalytic asymmetric hydrocarbonylation reactions.

Copper-Catalyzed Oxydifluoroalkylation of β,γ-Unsaturated Oximes for the Construction of Isoxazolines with a Difluoroalkyl Side Chain

AbstractA copper-catalyzed oxydifluoroalkylation of β,γ-unsaturated oximes has been developed. This reaction proceeded through a cascade of difluoroalkylation of alkene followed by a nucleophilic attack of the hydroxyl group of oximes. This protocol features mild reaction conditions, low-cost catalyst, and broad substrate scope, which provides a facile method to synthesize isoxazolines with a fluorinated side chain

Light-Driven Metal-Free Direct Deoxygenation of Alcohols under Mild Conditions.

SummaryHydroxyl is widely found in organic molecules as functional group and its deprivation plays an inevitable role in organic synthesis. However, the direct cleavage of Csp3-O bond in alcohols with high selectivity and efficiency, especially without the assistance of metal catalyst, has been a formidable challenge because of its strong bond dissociation energy and unfavorable thermodynamics. Herein, an efficient metal-free strategy that enables direct deoxygenation of alcohols has been developed for the first time, with hydrazine as the reductant induced by light. This protocol features mild reaction conditions, excellent functional group tolerance, and abundant and easily available starting materials, rendering selective deoxygenation of a variety of 1° and 2° alcohols, vicinal diols, and β-1 and even β-O-4 models of natural wood lignin. This strategy is also highlighted by its “traceless” and non-toxic by-products N2 and H2, as readily escapable gases. Mechanistic studies demonstrated dimethyl sulfide being a key intermediate in this transformation.

Iridium‐Catalyzed [4+2] Annulations of β‐Keto Sulfoxonium Ylides and o‐Phenylenediamines: Mild and Facile Synthesis of Quinoxaline Derivatives

A synthetic method for quinoxaline derivatives from the [4+2] annulation of β‐keto sulfoxonium ylides and o‐phenylenediamine by using (Cp*IrCl2)2 catalyst is described. This novel protocol features mild reaction conditions, moderate to excellent yields, wide substrate scope, and high functional‐group compatibility. Moreover, this cyclization strategy was successfully applied in late‐stage modification for structurally complex bioactive compounds.