Aerobic Oxidative Coupling Reaction Research Articles

Copper-catalyzed room-temperature cross-dehydrogenative coupling of secondary amides with terminal alkynes: a chemoselective synthesis of ynamides.

A copper-catalyzed aerobic oxidative cross-dehydrogenative coupling reaction between secondary amides and terminal alkynes has been developed. With the aid of ligands and 3 Å molecular sieves, ynamides can be efficiently synthesized at room temperature and conveniently scaled up. A legitimate mechanism involving nitrogen-centred radicals and copper trivalent intermediates has been proposed.

Low-Valent-Tungsten-Catalyzed Aerobic Oxidative Cross-Dehydrogenative Coupling Reaction.

A straightforward and convenient protocol was established for the synthesis of thiophosphates and 3-sulfenylated indoles via low-valent-tungsten-catalyzed aerobic oxidative cross-dehydrogenative coupling reactions. These reactions occur under mild conditions and simple operations with commercially available starting materials, processing the advantage of excellent atom and step economy, broad substrate scope, and good functional groups tolerance. Moreover, this transformation could be practiced on the gram scale, which exhibits great potential in the preparation of drug-derived or bioactive molecules.

Mechanistic Avenues in the Chan-Lam-Based Etherification Reaction: A Computational Exploration.

Ongoing advances in CuII -catalyzed aerobic oxidative coupling reactions between arylboronic esters and diverse heteroatom nucleophiles have strengthened the development of the general Chan-Lam (CL)-based reaction protocol, including C-O bond formation methodologies. In-depth mechanistic understanding of CL etherification with specific emphasis on different reaction routes and their energetics are still lacking, even though the reaction has been experimentally explored. Here, we present a DFT-guided computational study to unravel the mechanistic pathways of CL-based etherification. The computational findings provide some interesting insights into the fundamental steps of the catalytic cycle, particularly the rate-determining transmetalation event. An aryl boronic ester-coordinated, methoxide-bridged CuII intermediate that acts as resting state undergoes transmetalation with an activation barrier of 20.4 kcal mol-1 . The energy spans of the remaining fundamental steps leading to the methoxylated product are relatively low. The minor p-cresol product requires an additional 14.2 kcal mol-1 energy span to surmount in comparison to the favored route. Hammett studies for the substituted aryl boronic esters reveal higher reaction turnovers for electron-rich aryl systems. The results agree with previously reported spectroscopic and kinetic observations. For a series of alcohol substrates, it was observed that, except for cyclohexanol, moderate to high etherification turnovers are predicted.

Construction of a Novel TiO2‐Covalent‐Organic‐Framework Heterojunction for Highly Selective Photo‐Oxidation Coupling of Amines under Visible Light Irradiation

AbstractA novel heterojunction material constructed with titanium dioxide nanoparticles and covalent organic frameworks, TiO2@COF‐5 NPs, was designed and synthesized successfully from HHTP, PBBA and TiO2 under solvothermal conditions. Notably, the TiO2@COF‐5 heterojunction demonstrated excellent photocatalytic performance for the aerobic oxidative coupling reaction of benzylamines to N‐benzyl‐1‐phenyl methanimines under visible light irradiation, and both high conversions (up to 99 %) and high selectivity (99 %) were achieved for various benzylamines. The ameliorated photocatalytic performance might owe much to establishing the systematic coupling between the TiO2 nanoparticles and covalent organic frameworks, which could effectively extend the wavelength range of visible light absorption and increase more reactive active sites. This study might provide a versatile approach to combining covalent organic frameworks with inorganic semiconductors to give full play to the synergistic effect of catalysis.

5,8-Di-tert-butyl-2-hydroxy-1H-benzo[de]isoquinoline-1,3(2H)-dione—A New Lipophilic N-oxyl Radical Precursor

N-hydroxyimides are widely known as organocatalysts for aerobic oxidation and oxidative coupling reactions, in which corresponding imide-N-oxyl radicals play the role of catalytically active hydrogen atom abstracting species. The drawbacks of many N-hydroxyimides are poor solubility in low polarity solvents and limited activity in the cleavage of unactivated C–H bonds. To overcome these shortcomings, we have synthesized a new lipophilic N-hydroxyimide, 5,8-di-tert-butyl-2-hydroxy-1H-benzo[de]isoquinoline-1,3(2H)-dione, with high solubility in low-polarity solvents such as DCM. According to the EPR study, the stability of the corresponding imide-N-oxyl radical is comparable to that of the non-tert-butylated analogue, naphthalimide-N-oxyl radical. DFT calculations showed that the NO–H bond dissociation enthalpy (BDE) in the synthesized tert-butylated-N-hydroxynaphthalimide is one of the highest in N-hydroxyimide series, which corresponds to high hydrogen atom abstracting reactivity and may be useful in catalysis of strong C–H bond oxidative cleavage. The synthesized compound can be considered as catalyst for liquid-phase free-radical oxidation and oxidative coupling reactions in non-polar media where solubility was previously the limiting factor.

Visible-light induced C(sp3)-H arylation of glycine derivatives by cerium catalysis.

A Ce(III)-catalyzed, visible-light induced aerobic oxidative dehydrogenative coupling reaction between glycine derivatives and electron-rich arenes is disclosed. The protocol proceeds efficiently under mild conditions, providing an efficient method for the rapid synthesis of α-arylglycine derivatives without the need for an external photosensitizer and additional oxidant. Moreover, this protocol could be performed on a 5 mmol scale, without obvious reduction of the efficiency.

Synergic Palladium Catalysis for Aerobic Oxidative Coupling

AbstractAerobic oxidative coupling is a dehydrogenative organic transformation in which molecular oxygen acts as a re‐oxidant for the catalyst system. Pd has emerged as one of the most popular transition metal catalysts for such reactions. Combinations of Pd with other transition metal catalysts can also provide effective catalytic cycles together with highly atom‐ and step‐economical organic transformations. A synergic Pd catalyst system can promote such reactions with a high degree of efficiency based on a re‐oxidation step exhibiting improved kinetics in which two electrons are transferred from another transition metal. This occurs in conjunction with a lower energy barrier than that associated with direct re‐oxidation by molecular oxygen. This review highlights recent developments in aerobic oxidative coupling reactions catalyzed by synergic combinations of Pd with other transition metals. Highlighted reactions include dehydrogenative C−C bond formation such as arylation of arenes, heteroarenes, alkenes and dehydrogenative C−N and C−O bond formations with unsaturated hydrocarbons such as alkenes, 1,3‐dienes and allenes. Moreover, mechanistic insights into these aerobic reactions based on experimental, computational and optical studies are detailed.

Ni/g‐C3N4 Photocatalysis: Aerobic Oxidative Coupling Reaction Leading to Amidation of Aldehydes with Amines and C−N, C−O, and C−C Cross‐Coupling Reaction

AbstractDual nickel/carbon nitride (Ni/g‐C3N4) photocatalyst was employed for the synthesis a wide range of amide derivatives by cross‐coupling reaction of benzamides with aryl halides. Also, oxidative amidation of aromatic and aliphatic aldehydes with primary and secondary amines has been investigated. The synthesis of various derivatives of esters was performed based on the cross‐coupling reaction between carboxylic acids with aryl halides. Surprisingly, decarboxylation of carboxylic acid derivatives occurred under ambient conditions for the synthesis of biaryl derivatives. The reactions were run solvent‐free or in environmental benignant solvents, with recyclable photocatalysts under irradiation.

Copper-Catalyzed Phosphorylation of N,N-Disubstituted Hydrazines: Synthesis of Multisubstituted Phosphorylhydrazides as Potential Anticancer Agents.

An efficient copper-catalyzed aerobic oxidative cross-dehydrogenative coupling reaction for the synthesis of multisubstituted phosphorylhydrazides from N,N-disubstituted hydrazines and hydrogen phosphoryl compounds is accomplished. The reaction proceeds under mild conditions without the addition of any external oxidants and bases. This work reported here represents a direct P(═O)-N-N bond formation with the advantages of being operationally simple, good functional group tolerance, and high atom and step economy. Furthermore, the selected compounds exhibit potential inhibitory activity against tumor cells, which can be used in the field of screening of anticancer agents as new chemical entities.

Eosin-Y/Cu(OAc)2-catalyzed aerobic oxidative coupling reactions of glycine esters in the dark.

Catalytic aerobic oxidative coupling reactions of glycine esters with β-keto acids, indoles, naphthols, and pyrrole have been realized at ambient temperature via the manipulation of the ground state reactivity of eosin-Y in the presence of Cu(OAc)2 in the dark. This method delivers structurally diverse unnatural amino acid derivatives under mild reaction conditions. UV-vis absorption spectroscopy, cyclic voltammetry, X-ray photoelectron spectroscopy, high-resolution mass spectrometry, and control experiments were performed to formulate a plausible mechanistic pathway. The step economy, broad substrate scope, use of air as a green oxidant, and operationally simple set-up make this protocol highly appealing for both academic and industrial applications.

Cu‐Catalyzed Aerobic Oxidative Coupling of Tetrahydro‐β‐carbolines with Indoles

AbstractA copper‐catalyzed aerobic oxidative coupling reaction of tetrahydro‐β‐carbolines (THβCs) with indoles is reported for the first time. This room‐temperature catalytic strategy offers an efficient synthesis of the complex scaffold with an excellent chemoselectivity profile under mild reaction conditions.

Visible Light-Induced Oxidative Cross Dehydrogenative Coupling of Glycine Esters with β-Naphthols: Access to 1,3-Benzoxazines.

A direct aerobic oxidative dehydrogenative coupling reaction of glycine esters with β-naphthols has been achieved via the synergistic combination of photoredox catalysis and Lewis acid catalysis. A wide range of glycine esters and β-naphthols are suitable substrates for this reaction. A variety of 1,3-benzoxazines were obtained in good yields with excellent diastereoselectivities under mild reaction conditions. Moreover, this protocol could be performed on a gram-scale without considerable loss in activity.

Visible-light-enabled aerobic oxidative Csp3-H functionalization of glycine derivatives using an organic photocatalyst: access to substituted quinoline-2-carboxylates.

A practical visible-light-induced aerobic oxidative dehydrogenative coupling reaction of glycine derivatives with olefins has been developed to efficiently synthesize quinoline-2-carboxylates. This metal-free process proceeds smoothly under mild conditions and exhibits good tolerance of functional groups. Given the low cost of the catalyst and feedstock materials, the mild reaction conditions and the absence of hazardous byproducts, this protocol should find broad applications in the synthesis of quinoline-2-carboxylate derivatives.

Investigating the Oxidation Step in the CuCl2-Catalyzed Aerobic Oxidative Coupling Reaction of N-Aryl Tetrahydroisoquinolines.

The oxidative coupling of N-aryl tetrahydroisoquinolines with nucleophiles has inspired the development of novel C-H functionalization reactions as well as mechanistic studies. Here, we investigate the oxidation step that forms iminium ions as key intermediates in the method using CuCl2 as the catalyst and oxygen as the terminal oxidant. A strong electronic effect of substituents in the N-aryl ring was found by synthetic studies and a Hammett plot analysis, supporting initial electron transfer from the amine to Cu(II). The importance of the mechanism of oxidation on the substrate scope with differently substituted tetrahydroisoquinolines is discussed.

Poly (amic acid) Salt‐stabilized Au‐Ag Alloy Nanoparticles as Efficient and Recyclable Quasi‐homogeneous Catalysts for the Imines Synthesis from Alcohols and Amines in Water

AbstractWater‐soluble Au−Ag bimetallic nanoparticles with different Au/Ag molar ratios stabilized by poly (amic acid) salt (PAAS) were synthesized by a one‐pot method and characterized by ultraviolet‐visible spectrophotometer (UV‐vis), X‐ray diffractometer (XRD), X‐ray photoelectron spectroscope (XPS) and High‐Angle Annular Dark Field scanning transmission electron microscope (HAADF‐STEM). The Au−Ag/PAAS catalysts displayed high activity for the aerobic oxidative coupling reaction of alcohols and amines in water. Attributing to the synergistic effect between Au and Ag, the activity of the bimetallic catalysts was superior to that of the corresponding monometallic catalysts. The catalyst with an Au/Ag molar ratio of 6/1 showed the best catalytic performance, which could be easily recovered and reused without significant loss of activity for over 5 times due to the pH response of PAAS.

Synthesis, structural characterization, DFT calculations and biological properties of mono- and dinuclear nickel complexes with tetradentate transformed ligands by aerobic oxidative-coupling reactions

Reaction of nickel chloride with acetylacetone bis(salicylhydrazone) (L) (prepared in situ by condensation of acetylacetone with salicylhydrazide) in methanol results in the formation of air-sensitive nickel (II) complex of symmetrical tetradentate Schiff base [NiII(L)] (1). Air oxidation of 1 leads to the formation of dinuclear species [NiII(L-L)NiII] (2) where the ligand (L-L)4– is formed by oxidative C-C coupling at the central methylene group of the acetylacetone fragment of (L)2–. The same reaction in methanol/pyridine solution leads to oxidative C-N coupling forming a mesoionic [NiII(L-Py)](3). The use of Nickel acetylacetonate in methanol/pyridine or DMSO solution under aerobic conditions provide [NiII(L-O)(py)2](4), [NiII(L-O)(DMSO)2](5). In this case, the ligand (L)2– is partially oxidized to form (L-O) which is formed by oxidation of the central methylene group. The molecular structure of 1–5 have been determined by X-ray crystallography. The first three complexes 1, 2 and 3 have a square-planar geometry, while, 4 and 5 adopt octahedral geometry. In vitro antioxidant activities of compounds 1, 4 and 5 were evaluated against DPPH radical and hydrogen peroxide and were compared with standard antioxidant, ascorbic acid. Our results reveal that the three compounds exhibit excellent radical scavenging activities. DFT calculations have been performed on complexes 1–5 using the BP86 and B3LYP functionals to provide a complete rationalization of their structures and to describe their electronic structures elucidating the fundamental spin state and the Metal-Ligand interaction type.

Copper and cobalt co-catalyzed aerobic oxidative cross-dehydrogenative coupling reaction of (benzo)azoles

The dehydrogenative cross-coupling (CDC) reaction of diversely substituted azoles was realized by copper and cobalt co-catalysis under air conditions.

Visible Light‐Induced Aerobic Oxidative −H Arylation of Glycine Derivatives

AbstractA direct aerobic oxidative dehydrogenative coupling reaction of glycine derivatives with electron‐rich arenes has been accomplished via the synergistic combination of organic‐dye mediated photoredox catalysis and Lewis acid catalysis. This process exhibits good tolerance of functional groups and provides rapid synthesis of arylglycine derivatives at room temperature under an air atmosphere. Moreover, this protocol could be performed on a 10 mmol scale, without obvious reduction of the yield.magnified image

Mechanism of the Visible-Light-Mediated Copper-Catalyzed Coupling Reaction of Phenols and Alkynes.

A recent experimental study reported a visible-light-mediated aerobic oxidative coupling reaction of phenol with alkynes that produces hydroxyl-functionalized aryl ketones using inexpensive CuCl as catalyst under mild conditions. Here we apply the complete active space self-consistent field (CASSCF) method and multistate second-order perturbation (MS-CASPT2) theory in combination with density functional theory (DFT) to systematically explore the entire photocatalytic reaction between phenol and phenylacetylene in acetonitrile solution in the presence of molecular oxygen and CuCl. Our main findings are as follows: (1) The visible-light-driven conversion of phenylacetylene to PhCCCu(I) occurs thermally because of efficient excited-state deactivation to the S0 state. (2) The single electron transfer from PhCCCu(I) to molecular oxygen that leads to the PhCCCu(II) cation takes place in the T1 state after an efficient S1 → T1 intersystem crossing. (3) During the initial oxidation of phenol, molecular oxygen prefers to attack the para position of the phenol radical intermediate to produce 1,4-benzoquinone, which further reacts with PhCCCu(II) to generate para-hydroxyl-substituted aryl ketones; this is the origin of the experimentally observed regioselectivity. (4) The C≡C bond of the phenylacetylene moiety is not activated by the triplet-state single electron transfer from PhCCCu(I) to molecular oxygen but is cleaved at a later stage, in the [2+2] cycloaddition between PhCCCu(II) and 1,4-benzoquinone. (5) The substrate phenol plays an active role in several hydrogen transfer and decarboxylation reactions; the barriers to these phenol-assisted reactions are lower than those for the corresponding direct or water-assisted reactions, which explains the experimental finding that adding water does not enhance the photocatalytic reaction yield. In summary, while supporting the general features of the experimentally proposed mechanism, our computational study provides detailed mechanistic insights that should be useful for understanding and further improving visible-light-induced copper-catalyzed coupling reactions.

Synthesis of N, O-Spiroacetals and α-Arylfurans via Pd-Catalyzed Aerobic Oxidative 2,5-Aminoarylation and α-Arylation of N-[3-(2-Furanyl)propyl]- p-toluenesulfonamides with Boronic Acids.

Unsaturated N, O-spiroacetals and α-arylfurans were synthesized via palladium-catalyzed aerobic oxidative coupling reactions between N-[3-(2-furanyl)propyl]- p-toluenesulfonamides and boronic acids, with KF and KOAc as the respective additives. These reactions involve an unprecedented dearomatizing 2,5-aminoarylation and a direct α-arylation of furan rings, respectively, with O2 as the terminal oxidant.