Cross-dehydrogenative Coupling Research Articles

Aerobic Catalytic Cross-Dehydrogenative Coupling of Furans with Indoles Provides Access to Fluorophores with Large Stokes Shift.

Sustainability in chemical processes is a crucial aspect in contemporary chemistry with sustainable catalysis as a vital parameter of the same. There has been a renewed focus on utilizing earth-abundant metal catalysts to expand the repertoire of organic reactions. Furan is a versatile heterocycle of natural origin used for multiple applications. However, it has scarcely been used in cross-dehydrogenative coupling. In this work, we have explored the cross-dehydrogentive coupling of furans with indoles using commonly available, inexpensive FeCl3 ⋅ 6H2 O (<0.25 $/g) as catalyst in the presence of so called 'ultimate oxidant' - oxygen, without the need for any external ligand or additive. The reactions were found to be scalable and to work even under partially aqueous conditions. This makes the reaction highly economical, practical, operationally simple and sustainable. The methodology provides direct access to π-conjugated short oligomers consisting of furan, thiophene and indole. These compounds were found to show interesting fluorescence properties with remarkably large Stokes shift (up to 205 nm). Mechanistic investigations reveal that the reaction proceeds through chemoselective oxidation of indole by the metal catalyst followed by nucleophilic trapping by furan.

Direct Formation of C-C, C-N, and C-O Bonds in Dihydroquinazolines via Hypervalent Iodine(III)-Mediated sp3 C-H Functionalization.

A hypervalent iodine(III)-mediated cross-dehydrogenative coupling reaction for the direct formation of C-C, C-N, and C-O bonds in dihydroquinazolines has been developed. This one-pot method allows for the synthesis of C4-disubstituted dihydroquinazolines as well as C4-spirolactam, spirolactone, and spiroindene dihydroquinazolines in moderate to high yields.

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.

Mechanistic study on the reductive elimination of (aryl)(fluoroaryl)palladium complexes: a key step in regiospecific dehydrogenative cross-coupling.

Cross-dehydrogenative coupling (CDC) reactions have attracted attention as short-step synthetic methods for C-C bond formation. Recently, we have developed CDC reactions between naphthalene and fluorobenzene. Rather than exhibiting general regioselectivity, this reaction proceeds selectively at the β-position of naphthalene. In this study, investigation using model complexes as reaction intermediates revealed that the origin of the unique selectivity is the exclusive occurrence of reductive elimination at the β-position. Detailed studies on the reductive elimination showed that the steric hindrance of the naphthyl group and the electron-withdrawing properties of fluorobenzene determine the position at which the reductive elimination reaction proceeds. These results show that the selectivity of the C-H functionalisation of polycyclic aromatic hydrocarbons (PAHs) is determined not by the C-H cleavage step, but by the subsequent reductive elimination step. The regioselective CDC reaction was adaptable to various PAHs but was less selective for pyrene with extended π-conjugation. In fluorobenzene substrates, the F atoms at the two ortho positions of the C-H moiety are necessary for high selectivity. The substrate ranges are in good agreement with the proposed mechanism, in which the reductive elimination step determines the regioselectivity.

Silver(I)-catalyzed highly para-selective phosphonation of 2-aryloxazolines.

A silver-catalyzed phosphonation of 2-aryloxazolines has been accomplished. This protocol provides highly regioselective access to para-phosphonation products with good functional group tolerance and moderate to good yields via cross-dehydrogenation coupling. Mechanistic studies have shown that para-phosphonation products are obtained via a radical pathway. Furthermore, the directing oxazoline group in the para-phosphonation products is removable and can be converted to benzoic esters.

Aerobic oxidative C-C bond formation through C-H bond activation catalysed by flavin and iodine.

We report a metal/light-free aerobic oxidative C-C bond formation using sp3 C-H bond activation of tetrahydroisoquinolines catalyzed by flavin and iodine. The dual catalytic system enabled the oxidative Mannich and aza-Henry reactions by the cross-dehydrogenative coupling between two sp3 C-H bonds. Furthermore, the flavin-iodine-coupled catalysis was applied to the synthesis of pyrrolo[2,1-a]isoquinolines through the sequential oxidative 1,3-dipolar cycloaddition and dehydrogenative aromatization. The biomimetic flavin catalysis efficiently activates molecular oxygen; thus the non-metal dual catalytic system enables green oxidative transformation using molecular oxygen as an environmentally friendly terminal oxidant which generates benign water.

Preparation of an OHCP nanofiber photocatalyst for cross-dehydrogenation coupling reactions

Phloxine B (PHB) exhibited high catalytic efficiency in cross-dehydrogenation coupling (CDC) reactions.

Iodine-enabled organoelectrocatalysis: enantioselective cross dehydrogenative coupling of sulfides and aldehydes

A method for the direct asymmetric α-sulfenylation of aldehydes with sulfides was developed.

Hollow anatase TiO2 tetrakaidecahedral crystals with an active {001}/{110} redox interface toward high-performance photocatalytic activity.

The existence of the oxidation/reduction interface can promote the performance of a photocatalyst, due to its effect on the separation of photogenerated carriers and the surface reactivity. However, it is difficult to construct two sets of oxidation/reduction interfaces in a single crystal and compare their separation efficiency for photogenerated carriers. Introducing a high proportion of active facets into the co-exposed facets is even more challenging. Herein, a hollow anatase TiO2 tetrakaidecahedron (HTT) with two sets of oxidation/reduction interfaces ({001}/{101} and {001}/{110}) is synthesized by directional chemical etching. Theoretical and experimental results indicate that the {001}/{110} interface is a dominant oxidation/reduction interface, showing a better promotion on the separation of photogenerated carriers than the {001}/{101} interface. In the HTT, the ratio of dominant {001}/(110) is increased and the proportion of the active {110} facet is about 40% (generally about 15%). Therefore, the HTT shows excellent catalytic activity for photocatalytic reductive (hydrogen production) and oxidative (selective oxidation of sulfides) reactions. The HTT also demonstrates favorable photocatalytic activity for the cross-dehydrogenative coupling reaction, where both photogenerated electrons and photogenerated holes are involved, further verifying its high separation efficiency of photogenerated carriers and surface reactivity. This work provides an important guideline for developing advanced structures with a predetermined interface toward desired applications.

Transition-metal-free access to benzyl ethers via aerobic cross-dehydrogenative coupling of benzylic C(sp3)–H bonds with alcohols

We have developed an efficient and green cross-coupling reaction for alkoxylation of the primary benzylic C(sp3)–H bond. KOtBu was used as a catalyst and O2 was used as the sole oxidant in the methoxylation of the primary benzylic C–H bond.

Metal-free visible light-induced cross-dehydrogenative coupling of benzocyclic imines with water/P(O)H compounds: efficient access to functionalized benzazepines/ones

A metal-free visible light-induced cross-dehydrogenative coupling of aldimines with nucleophiles in a one-pot fashion is first reported, which features high efficiency,the absence of external oxidants, and mild and redox-neutral reaction conditions.

Metal- and photosensitizer-free cross-dehydrogenative coupling through photoinduced energy transfer

This study introduces a novel, eco-friendly method for Minisci alkylation without harmful catalysts, advancing sustainable pharmaceutical synthesis through energy transfer from heteroarenes to peroxide, offering significant environmental benefits.

Palladium-catalyzed cross-dehydrogenative coupling of (hetero)arenes

A general and authoritative literature overview on Pd-catalyzed cross-dehydrogenative coupling reactions of (hetero)arenes from the origins to 2023, where not only the synthetic aspects were described but also the most relevant mechanistic features.

Correction: Ethanol-assisted mechanochemical asymmetric cross-dehydrogenative coupling reaction with recoverable chiral amine/NaCl for accessing chiral α-alkyl α-glycine derivatives

Correction for ‘Ethanol-assisted mechanochemical asymmetric cross-dehydrogenative coupling reaction with recoverable chiral amine/NaCl for accessing chiral α-alkyl α-glycine derivatives’ by Jingbo Yu et al., Green Chem., 2024, https://doi.org/10.1039/d4gc00947a.

Enantioselective cross-dehydrogenative coupling enabled by organocatalysis

Organocatalytic enantioselective cross-dehydrogenative coupling reaction provides a great opportunity for the synthesis of highly enantioenriched molecules. In this review, recent progress in this field is summarized.

Asymmetric 1,2-diaxial synthesis of bi-(hetero)aryl benzofulvene atropisomers via transient directing group-assisted dehydrogenative coupling.

The efficient cross-dehydrogenative coupling of electronically rich and sterically congested benzofulvene with bi-(hetero)aryl moieties to construct an axially chiral benzofulvene core remains a formidable task. In this study, we describe a highly efficient and practical palladium-catalyzed approach for atroposelective bi-(hetero)aryl benzofulvene synthesis, achieving excellent enantioselectivity with moderate yields. This protocol offers a remarkable opportunity for the direct regio- and enantioselective conversion of C-H bonds of benzofulvene to C-C bonds. Furthermore, the protocol permits the incorporation of benzofulvene with a 4-phenyl coumarin core, enabling access to a novel class of axially chiral coumarins.

Ethanol-assisted mechanochemical asymmetric cross-dehydrogenative coupling reaction with recoverable chiral amine/NaCl for accessing chiral α-alkyl α-glycine derivatives

Ethanol-assisted grinding effectively facilitated aerobic asymmetric cross-dehydrogenative coupling of glycine esters/amides with ketones/aldehydes, deploying reusable chiral amine/NaCl for rapid synthesis of chiral α-alkyl α-glycine derivatives.

Photoinduced decarboxylative germylation of α-fluoroacrylic acids: access to germylated monofluoroalkenes.

Herein, a novel strategy is presented for the photoinduced decarboxylative and dehydrogenative cross-coupling of a wide range of α-fluoroacrylic acids with hydrogermanes. This methodology provides an efficient and robust approach for producing various germylated monofluoroalkenes with excellent stereoselectivity within a brief photoirradiation period. The feasibility of this reaction has been demonstrated through gram-scale reaction, conversion of germylated monofluoroalkenes, and modification of complex organic molecules.

Rationally designed C-3 sulfenylated 2-phenyl-4H-pyrido[1,2-a]pyrimidin-4-one based fluorescent probe for recognition of Fe3+

Cross-dehydrogenative coupling (CDC) efficiently constructs complex organic molecules by directly coupling two C-H bonds from different substrates. This enables the functionalisation of existing chromophores with different substituents, facilitating efficient sensor development. Electronically diverse C-3 sulfenylated 2-phenyl-4H-pyrido[1,2-a]pyrimidin-4-ones (3a-3d) were synthesised using iodine mediated CDC protocol and structurally characterised using FT-IR, 1H and 13C NMR and mass spectrometry technique. Single crystal X-ray diffraction technique was utilised for establishing the molecular structure of 3d. The absorption and emission intensity for all the synthetics were recorded in the range of 365-375 and 406-509 nm, respectively in solvents of varying polarity. Compound 3b, with distinct dispersion of the frontier molecular orbitals due to ring extension, showed exceptional absorption and emission intensity in water and methanol. All the sensing applications of 3b were investigated using water/methanol (1:4; v/v) as the solvent system. An abrupt increase in the absorption intensity with a decrease in emission maxima of 3b was observed upon Fe(NO3)3.9H2O addition. A detection limit of 1.27 × 10−6 M, low response time and thermal stability served as some of the characteristic features which established the probe as a potential sensor for Fe3+ ion. Further, the stoichiometry and binding constant of the complex was determined by Benesi-Hildebrand and Job's plot.

Flavin‐Catalyzed Aerobic Oxidative C−C Bond Formation by Metal/Light‐Free Cross‐Dehydrogenative Coupling

AbstractBiomimetic flavin catalysts enable green and selective aerobic oxidative transformations. However, most previous studies tended to focus on reproducing the enzymatic function of flavin monooxygenase, thereby limiting the applications of flavin catalysts to oxygen‐atom transfer reactions. We herein report a cross‐dehydrogenative coupling (CDC) between the sp3 C−H bond of tetrahydroisoquinolines and the sp3 and sp2 C−H bonds of carbon nucleophiles, such as α‐methylene carbonyl compounds, nitromethane, and indoles, for C−C bond formation promoted by flavin catalysts. Flavin catalysis enables the oxidative C−H activation of tetrahydroisoquinolines and the efficient activation of molecular oxygen (1 atm) under mild and metal/light‐free conditions, thus facilitating a green aerobic CDC that generates benign water as the sole by‐product.