Electrochemical Skeletal Indole Editing via Nitrogen Atom Insertion by Sustainable Oxygen Reduction Reaction.

Skeletal molecular editing gained considerable recent momentum and emerged as a uniquely powerful tool for late-stage diversifications. Thus far, superstoichiometric amounts of costly hypervalent iodine(III) reagents were largely required for skeletal indole editing. In contrast, we herein show that electricity enables sustainable nitrogen atom insertion reactions to give bio-relevant quinazoline scaffolds without stoichiometric chemical redox-waste product.

Direct Synthesis of C4-Acyl Indoles via C-H Acylation.

The direct synthesis of C4-acyl indoles deprived of C2 and C3 substituents has proven to be challenging, with scarce efficient synthetic routes being reported. Herein, we disclose a highly site-selective palladium-catalyzed C-H acylation for the construction of C4-acyl indoles via a Catellani-Lautens cyclization strategy. In addition, we systematically studied the C-H acylation mechanism of iodoaniline through density functional theory (DFT) calculations and combined experimental results to elucidate the principle of high chemoselectivity brought by triazine benzoate as an acylation reagent.

Chelation-Assisted Iron-Catalyzed C-H Activations: Scope and Mechanism.

ConspectusTo improve the resource economy of molecular syntheses, researchers have developed strategies to directly activate otherwise inert C-H bonds, thus avoiding cumbersome and costly substrate prefunctionalizations. During the past two decades, remarkable progress in coordination chemistry has set the stage for developing increasingly viable metal catalysts for C-H activations. Despite remarkable advances, C-H activations are largely dominated by precious 4d and 5d transition metal catalysts based primarily on palladium, ruthenium, iridium, and rhodium, thus decreasing the inherent sustainable nature of the C-H activation approach.

Template Synthesis to Solve the Unreachable C-H Functionalization Reaction of Aryl Iodide.

This report describes the use of a simple Pd/NBE catalytic system to achieve C-H oxylation and phosphonylation and other functionalizations of aryl iodide through templated conversion reactions. Dimethylamine is introduced in the -site of aryl iodide through C-H amination, and aryl dimethylamine is quickly converted to methyl quaternary ammonium salt precipitation. Methyl quaternary ammonium salt avoids Hofmann elimination in subsequent functionalization.

Polymer up-cycling by mangana-electrocatalytic C(sp)-H azidation without directing groups.

The chemical up-cycling of polymers into value-added materials offers a unique opportunity to place plastic waste in a new value chain towards a circular economy. Herein, we report the selective up-cycling of polystyrenes and polyolefins to C(sp)-H azidated materials under electrocatalytic conditions. The functionalized polymers were obtained with high retention of mass average molecular mass and high functionalization through chemo-selective mangana-electrocatalysis.

Reusable Pd@PEG Catalyst for Aerobic Dehydrogenative C-H/C-H Arylations of 1,2,3-Triazoles.

Dehydrogenative C-H arylations of 1,2,3-triazoles were accomplished with the aid of a reusable palladium catalyst in PEG. The widely applicable oxidative palladium catalysis enabled the synthesis of fully decorated 1,2,3-triazoles with a broad functional-group tolerance and ample substrate scope. The sustainability of the aerobic C-H arylation was reflected by the use of PEG as green reaction medium and demonstrated by recycling studies of the catalyst and the reaction medium.

Micellar Catalysis for Ruthenium(II)-Catalyzed C-H Arylation: Weak-Coordination-Enabled C-H Activation in H O.

Chemoselective C-H arylations were accomplished through micellar catalysis by a versatile single-component ruthenium catalyst. The strategy provided expedient access to C-H-arylated ferrocenes with wide functional-group tolerance and ample scope through weak chelation assistance. The sustainability of the C-H arylation was demonstrated by outstanding atom-economy and recycling studies.

MnCl-Catalyzed C-H Alkylation on Azine Heterocycles.

Low-valent manganese-catalyzed C-H alkylation of pyridine derivatives with both primary and challenging secondary alkyl halides was established by amide assistance. The strategy provided expedient access to alkylated pyridines with wide functional group tolerance and ample scope through weak chelation. Mechanistic studies provided strong support for a rate-determining C-H activation and a SET-type C-X scission.

3d Transition Metals for C-H Activation.

C-H activation has surfaced as an increasingly powerful tool for molecular sciences, with notable applications to material sciences, crop protection, drug discovery, and pharmaceutical industries, among others. Despite major advances, the vast majority of these C-H functionalizations required precious 4d or 5d transition metal catalysts. Given the cost-effective and sustainable nature of earth-abundant first row transition metals, the development of less toxic, inexpensive 3d metal catalysts for C-H activation has gained considerable recent momentum as a significantly more environmentally-benign and economically-attractive alternative.

Arene-Ligand-Free Ruthenium(II/III) Manifold for meta-C-H Alkylation: Remote Purine Diversification.

meta-Selective C-H alkylations of bioactive purine derivatives were accomplished by versatile ruthenium catalysis. Thus, the arene-ligand-free complex [Ru(OAc) (PPh ) ] enabled remote C-H functionalizations with ample scope and excellent levels of chemo- and positional selectivities. Detailed experimental and computational mechanistic studies provided strong support for a facile C-H activation within a ruthenium(II/III) manifold.

Synergistic Manganese(I) C-H Activation Catalysis in Continuous Flow: Chemoselective Hydroarylation.

Chemoselective hydroarylations were accomplished by a novel synergistic Brønsted acid/manganese(I)-catalyzed C-H activation manifold. Thus, alkynes bearing O-leaving groups could, for the first time, be employed for C-H alkenylations without concurrent β-O elimination, thereby setting the stage for versatile late-stage diversifications. Also described is the first manganese-catalyzed C-H activation in continuous flow, thus enabling efficient hydroarylations within only 20 minutes.

Ruthenium(II)-catalysed remote C-H alkylations as a versatile platform to meta-decorated arenes.

The full control of positional selectivity is of prime importance in C-H activation technology. Chelation assistance served as the stimulus for the development of a plethora of ortho-selective arene functionalizations. In sharp contrast, meta-selective C-H functionalizations continue to be scarce, with all ruthenium-catalysed transformations currently requiring difficult to remove or modify nitrogen-containing heterocycles.

meta-C-H Bromination on Purine Bases by Heterogeneous Ruthenium Catalysis.

Methods for positionally selective remote C-H functionalizations are in high demand. Herein, we disclose the first heterogeneous ruthenium catalyst for meta-selective C-H functionalizations, which enabled remote halogenations with excellent site selectivity and ample scope. The versatile heterogeneous Ru@SiO catalyst was broadly applicable and could be easily recovered and reused, which set the stage for the direct fluorescent labeling of purines.

C-H arylations of 1,2,3-triazoles by reusable heterogeneous palladium catalysts in biomass-derived γ-valerolactone.

C-H arylations were accomplished with a user-friendly heterogeneous palladium catalyst in the biomass-derived γ-valerolactone (GVL) as an environmentally-benign reaction medium. The user-friendly protocol was characterized by ample substrate scope and high functional group tolerance in the C-H arylation of 1,2,3-triazoles, and the palladium catalyst could be recycled and reused in the C-H activation process.

Cobalt-Catalyzed Oxidase C-H/N-H Alkyne Annulation: Mechanistic Insights and Access to Anticancer Agents.

Cp*-free cobalt-catalyzed alkyne annulations by C-H/N-H functionalizations were accomplished with molecular O2 as the sole oxidant. The user-friendly oxidase strategy proved viable with various internal and terminal alkynes through kinetically relevant C-H cobaltation, providing among others step-economical access to the anticancer topoisomerase-I inhibitor 21,22-dimethoxyrosettacin. DFT calculations suggest that electronic effects control the regioselectivity of the alkyne insertion step.

Single-Component Phosphinous Acid Ruthenium(II) Catalysts for Versatile C-H Activation by Metal-Ligand Cooperation.

Well-defined ruthenium(II) phosphinous acid (PA) complexes enabled chemo-, site-, and diastereoselective C-H functionalization of arenes and alkenes with ample scope. The outstanding catalytic activity was reflected by catalyst loadings as low as 0.75 mol %, and the most step-economical access reported to date to angiotensin II receptor antagonist blockbuster drugs.

Ruthenium Oxidase Catalysis for Site-Selective C-H Alkenylations with Ambient O2 as the Sole Oxidant.

Ruthenium(II) oxidase catalysis by direct dioxygen-coupled turnover enabled step-economical oxidative C-H alkenylation reactions at ambient pressure. Versatile ruthenium(II) biscarboxylate catalysts displayed ample substrate scope and proved applicable to weakly coordinating and removable directing groups. The twofold C-H functionalization strategy was characterized by exceedingly mild reaction conditions as well as excellent positional selectivity.

N-Acyl Amino Acid Ligands for Ruthenium(II)-Catalyzed meta-C-H tert-Alkylation with Removable Auxiliaries.

Acylated amino acid ligands enabled ruthenium(II)-catalyzed C-H functionalizations with excellent levels of meta-selectivity. The outstanding catalytic activity of the ruthenium(II) complexes derived from monoprotected amino acids (MPAA) set the stage for the first ruthenium-catalyzed meta-functionalizations with removable directing groups. Thereby, meta-alkylated anilines could be accessed, which are difficult to prepare by other means of direct aniline functionalizations.

Ruthenium(II)-catalyzed C-H activation/alkyne annulation by weak coordination with O2 as the sole oxidant.

Aerobic oxidative CH functionalizations of weakly coordinating benzoic acids have been accomplished with versatile ruthenium(II) biscarboxylates under ambient oxygen or air. Mechanistic studies identified the key factors controlling the elementary step of the oxidation of the ruthenium(0) complex.