Oxidative Cross-dehydrogenative Coupling Research Articles

Enantioselective Nickel-Electrocatalyzed Cross-Dehydrogenative α- and γ-Nitroalkylation.

Asymmetric catalytic versions of electricity-driven processes hold immense potential for the sustainable preparation of chiral compounds. However, the involvement of anodic oxidative cross-dehydrogenative coupling events between two distinct nucleophiles makes it challenging for a chiral catalyst to regulate the stereochemistry of the products. Our current electrocatalytic strategy for enantioconvergent cross-dehydrogenative α- and γ-nitroalkylation via radical-based pathways produces an array of enantioenriched nitroesters without supplementary stoichiometric oxidants. Mechanistic investigations reveal that the nickel catalyst plays a key role in both the electrochemical activation of the substrates and the stereoselectivity-defining events, affording the electrochemically generated Lewis acid-bound α-carbonyl radicals to interact with in situ-generated nitronate anions in a stereoselective manner. This electrocatalytic approach enables transformations that are highly challenging under thermal conditions, such as umpolung reactivity with readily available substrates, all-carbon quaternary stereocenter creation, and the control of remote stereochemistry.

Palladium-Catalyzed Weak Chelation-Assisted Site-Selective C-H Arylation of N-Aryl Pyridones via 2-fold C-H Activation.

Palladium-catalyzed weak chelation-assisted oxidative cross-dehydrogenative coupling of arenes has been accomplished. The use of medicinally important pyridones as the intrinsic directing group, regioselectivity, 2-fold C-H activation, and late-stage modification of bioactive compounds are the important practical features.

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.

FeBr3-catalysed synthesis of 3-aroylimidazo[1,2-a]pyridine and 3,3'-(arylmethylene)bis(2-phenylimidazo[1,2-a]pyridines) derivatives from 2-arylimidazo[1,2-a]pyridines and aromatic aldehydes: an investigation about mechanistic insights.

In a new approach, a series of 3-aroylimidazo[1,2-a]pyridine derivatives were prepared in high yields. This approach revealed the direct Fe-catalyzed functionalization of imidazo[1,2-a]pyridine derivatives with aryl aldehydes via an aerobic oxidative cross-dehydrogenative coupling process. This transformation occurred in the presence of air, and FeBr3 served as a homogeneous Lewis catalyst. O2 was found to be the principal oxidant responsible for the method's success. Interestingly, when these reactions were carried out under an argon atmosphere, 3,3'-(arylmethylene)bis(2-phenylimidazo[1,2-a]pyridines) derivatives were prepared in good yields.

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.

Synthesis of 3-sulfenylindole derivatives from 4-hydroxy-2H-chromene-2-thione and indole using oxidative cross-dehydrogenative coupling reaction and anti-proliferative activity study of some of their sulfone derivatives

The synthesis of hitherto unreported 3-sulfenylindole derivatives is achieved from 4-hydroxy-2H-chromene-2-thione (1) and indole (2) by employing an oxidative cross-dehydrogenative coupling reaction using a combination of 10 mol% of molecular iodine and 1 equivalent of TBHP in DMSO at room temperature. Then, the 3-sulfenylindole derivatives 3a, 3b, 3d, 3f, 3 h, and 3 k were converted into their corresponding sulfone derivatives because of lead likeness properties. Subsequently, a target prediction and docking study of six sulfone derivatives (5a-f) was performed, and four sulfones, namely 5a, 5d, 5e, and 5f, were selected for further in-vitro studies. The four sulfones mentioned above exhibited prominent anti-proliferative activity on breast cancer (MCF7) cell lines. In addition, this reaction was exergonic through quantum chemical analysis of the mechanistic steps. The salient features of this reaction are mild reaction conditions, good yields, and broad substrate scope.

Oxidative Cross Dehydrogenative Coupling of N-Heterocycles with Aldehydes through C(sp3)-H Functionalization.

Existing methodologies for metal-catalyzed cross-couplings typically rely on preinstallation of reactive functional groups on both reaction partners. In contrast, C-H functionalization approaches offer promise in simplification of the requisite substrates; however, challenges from low reactivity and similar reactivity of various C-H bonds introduce considerable complexity. Herein, the oxidative cross dehydrogenative coupling of α-amino C(sp3)-H bonds and aldehydes to produce ketone derivatives is described using an unusual reaction medium that incorporates the simultaneous use of di-tert-butyl peroxide as an oxidant and zinc metal as a reductant. The method proceeds with a broad substrate scope, representing an attractive approach for accessing α-amino ketones through the formal acylation of C-H bonds α to nitrogen in N-heterocycles. A combination of experimental investigation and computational modeling provides evidence for a mechanistic pathway involving cross-selective nickel-mediated cross-coupling of α-amino radicals and acyl radicals.

Oxidative cross dehydrogenative coupling directed carbamates synthesis using Cu(II) pincer complex as active catalyst under mild reaction condition

AbstractDevelopment of an air‐stable and cheap transition metal‐based catalyst for the formation of carbamates via the cross‐coupling reaction of various 2‐carbonyl substituted phenolic derivatives or 1,3‐diketo derivatives with N,N‐disubstituted formamides (C(sp2)O bond formation) under mild conditions is the key focus of synthetic chemists. In this context, we have developed a novel benzothiazole appended 2,6‐di picolinamide‐based Cu(II) complex for the facile generation of carbamates at a slightly elevated temperature (50°C) with a short reaction time and low catalyst loading (0.5 mol%) for the first time. The synthesized complex was well characterized by ultraviolet–visible, infrared, electron paramagnetic resonance spectroscopy, cyclic voltammetry, high‐resolution mass spectrometry (HRMS), as well as by single crystal X‐ray diffraction analysis. A wide range of aromatic carbamates was synthesized using complex 1 in good/excellent yield with decent functional group tolerance under mild conditions. Control experiments suggest that the reaction proceeds via the radical mechanism, and the formation of radical‐mediated intermediates was confirmed by the gas chromatography (GC), GCMS and HRMS. The use of low cost and environmentally benign catalysts in mild conditions along with the tolerance of a wide range of functional groups makes this an easy synthetic approach for the development of carbamates.

Aerobic cross-dehydrogenative coupling of toluenes and o-phenylenediamines by flavin photocatalysis for the facile synthesis of benzimidazoles.

Herein, we demonstrate a green atom-economical synthesis of benzimidazoles via the flavin-photocatalysed aerobic oxidative cross-dehydrogenative coupling of toluenes and o-phenylenediamines. The proposed metal-free reaction proceeds in methanol/H2O under visible light irradiation by consuming only molecular oxygen from atmospheric air and produces only water as waste.

Cooperative photocatalysis and l-/d-proline catalysis enables enantioselective oxidative cross-dehydrogenative coupling of acyclic benzylic secondary amines with ketones

We developed an enantioselective cross-dehydrogenative coupling of acyclic benzylic secondary amines with ketones by combining photocatalysis and l-/d-proline catalysis.

Organophotoredox-Catalyzed Cross-Dehydrogenative Sulfonamidation of Indoles and Other Heterocycles.

The visible light-triggered regioselective synthesis of 2-sulfonamidoindoles and other 2-sulfonamido heteroarenes is accomplished by the oxidative cross-dehydrogenative coupling of indoles (heteroarenes) with di-p-toluenesulfonamide or N-aryl-p-toluenesulfonamides. The reaction was catalyzed by eosin-Y through a photoredox route. Detailed mechanistic studies based on control reactions, cyclic voltammetry, and fluorescence quenching have been reported for the elucidation of the mechanistic cycle and revealed that a nitrogen-centered radical is generated, followed by regioselective addition to the heteroarene. The operationally simple, straightforward methodology and easy availability of the starting materials allow for the synthesis of a wide range of 2-amidated indoles as well as other heterocyclic compounds.

Metal-Free Atom-Economical Synthesis of Tetra-Substituted Imidazoles via Flavin-Iodine Catalyzed Aerobic Cross-Dehydrogenative Coupling of Amidines and Chalcones.

Herein, we demonstrated the oxidative cross-dehydrogenative coupling between amidines and chalcones catalyzed by flavin and iodine. The riboflavin-iodine catalytic system played multiple roles in substrate- and O2-activation, enabling the facile and atom-economical synthesis of tetra-substituted imidazoles in good yields (60-87%). This metal-free reaction consumed only 1 equiv of molecular oxygen and generated 2 equiv of environmentally benign H2O as the only byproduct.

Copper-catalyzed oxidative cross-dehydrogenative coupling (CDC) reaction of alcohols with secondary phosphine oxides

A copper-catalyzed oxidative cross-dehydrogenative coupling (CDC) strategy of secondary phosphine oxides and alcohols for the synthesis of various phosphinate esters was proposed. Under the mild reaction conditions (CuCl2·2H2O/K2S2O8, at room temperature for 3–12 h under air), a variety of substrates were well-tolerated and afforded the desirable compounds in moderate to excellent yields.

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.

Cyanomethylation of the Benzene Rings and Pyridine Rings via Direct Oxidative Cross-Dehydrogenative Coupling with Acetonitrile.

A novel and efficient approach for the amine-directed dehydrogenative C(sp2)-C(sp3) coupling of arylamines with acetonitrile was reported by using FeCl2 as the catalyst. Substituted anilines, aminopyridines, naphthylamines, and some nitrogen-containing heterocyclic arylamines react with inactive acetonitrile to form the corresponding arylacetonitriles in moderate to good yields. This protocol features nontoxic iron catalysis, efficient atom economy, nonprefunctionalized starting materials, good regioselectivity, and excellent compatibility of functional groups and aromatic rings, providing a novel, straightforward, and green approach toward arylacetonitriles.

Efficient one-step synthesis of 3-(indol-2-yl)quinoxalin-2(1H)-ones via electrochemical oxidative cross-dehydrogenative coupling

A novel and efficient synthetic strategy for 3-(indol-2-yl)quinoxalin-2(1H)-ones was developed via electrochemical oxidative cross-dehydrogenative coupling of indoles and quinoxalin-2(1H)-ones.

A novel quinoline-based NNN-pincer Cu(II) complex as a superior catalyst for oxidative esterification of allylic C(sp3)-H bonds.

We report for the first time that the quinoline-based NNN-pincer Cu(II) complex acts as an air stable superior catalyst for the oxidative cross-coupling of the allyl sp3 C-H bond with an acid for the synthesis of allyl esters in a homogeneous system at ambient temperature. The synthesized catalyst, 1, has been well characterized by various analytical techniques (HRMS, single crystal X-ray diffraction, CV, EPR, UV-vis spectroscopy) and showed excellent catalytic activity for the oxidative esterification of allylic C(sp3)-H bonds at 40 °C within a very short period of time (1 h) using only 1 mol% of the catalyst. A wide variety of aromatic allylic esters were synthesized in moderate to good yields, which could be extended to aliphatic allyl esters as well.

Cascade Reaction of 2-Naphthols and Azirines: One-Pot Synthesis of C-3 Naphthol-Substituted Benzo[e]indoles.

A copper-catalyzed annulation of 3-aryl-2H-azirines with 2-naphthols has been developed for the rapid assembly of C-3-naphthol-substituted benzo[e]indoles in one pot. This cascade reaction was realized through dearomatic nucleophilic ring opening of azirine, intramolecular cyclization, and oxidative cross-dehydrogenative coupling to furnish the important unreported π-expanded naphthol/benzo[e]indole biaryls.

Electrochemical Oxidation Cross Dehydrogenative Coupling of Enamines and Thiophenols for the Synthesis of Vinyl Sulfides

AbstractA direct electrochemical oxidative cross dehydrogenative coupling reaction between enamines and thiophenols has been demonstrated. This strategy provides an effective, more economical, and environmentally friendly method to construct the C(sp2)‐S bond in the absence of chemical oxidants and transition metal catalysts. A variety of enamines and (hetero)aryl thiols are compatible with this transformation to afford the corresponding vinyl sulfides in moderate to excellent yields under undivided electrolytic cell conditions.

Metal-free regioselective C5-cyanoalkylation of the 8-aminoquinolineamides/sulfonamides via oxidative cross-dehydrogenative coupling with alkylnitriles

A practical, versatile and Metal-free regioselective C5-cyanoalkylation of the 8-aminoquinolineamides/sulfonamides with acetonitrile has been described.