LG

We reported an electrocatalytic strategy to upgrade plastic and biomass to formamide in the presence of NH₃ over a WO₃ catalyst under ambient conditions. Facilitated by nucleophilic attack of in situ formed nitrogen radicals from NH₃, the C−C bond in PET-derived ethylene glycol and biomass-derived polyols were effectively cleaved with C−N bond formation.

Abstract

Electrocatalytic upgrading of wasted plastic and renewable biomass represents a sustainable method to produce chemicals but is limited to carbohydrates, leaving other value-added chemicals, such as organonitrogen compounds, being scarcely explored. Herein, we reported an electrocatalytic oxidation strategy to transform polyethylene terephthalate (PET) plastic-derived ethylene glycol (EG) and biomass-derived polyols into formamide, in the presence of ammonia (NH₃) over a tungsten oxide (WO₃) catalyst. Taking EG-to-formamide as an example, we achieved a high formamide productivity of 537.7 μmol cm⁻² h⁻¹ with FE of 43.2 % at a constant current of 100 mA cm⁻² in a flow electrolyzer with 12-h test, representing a more advantageous performance compared with previous reports for formamide electrosynthesis. Mechanistic understanding revealed that the cleavage of the C−C bond in the EG was facilitated by nucleophilic attack of in situ formed nitrogen radicals from NH₃, with resultant C−N bond construction and eventually formamide production. Furthermore, this strategy can be extended to transformation of PET bottle and a series of biomass-derived polyols with carbon number from three (glycerol) to six (glucose), producing formamide with high efficiencies. This work demonstrates a sustainable upgrading strategy of plastic and biomass that may have implications to more value-added chemicals production beyond carbohydrates.

Decarboxylative C(sp²)−C(sp³) bond formation using a metallaphotoredox approach is a key method for rapidly building molecular complexity. In this work, we demonstrate that graphitic carbon nitride, a heterogeneous semiconductor, can act as a suitable photocatalyst to induce decarboxylative bond formation. A broad scope of coupling partners is presented, in addition to photocatalyst recycling, analysis, and mechanistic investigations.

Abstract

The development of robust and reliable methods for the construction of C(sp²)−C(sp³) bonds is vital for accessing an increased array of structurally diverse scaffolds in drug discovery and development campaigns. While significant advances towards this goal have been achieved using metallaphotoredox chemistry, many of these methods utilise photocatalysts based on precious-metals due to their efficient redox processes and tuneable properties. However, due to the cost, scarcity, and toxicity of these metals, the search for suitable replacements should be a priority. Here, we show the use of commercially available heterogeneous semiconductor graphitic carbon nitride (gCN) as a photocatalyst, combined with nickel catalysis, for the cross-coupling between aryl halide and carboxylic acid coupling partners. gCN has been shown to engage in single-electron-transfer (SET) and energy-transfer (EnT) processes for the formation of C−X bonds, and in this manuscript we overcome previous limitations to furnish C−C over C−O bonds using carboxylic acids. A broad scope of both aryl halides and carboxylic acids is presented, and recycling of the photocatalyst demonstrated. The mechanism of the reaction is also investigated.

The ion-pair [Ph₃C]⁺[B(C₆F₅)₄]⁻-mediated electrocatalytic benzylic C−H oxidation is described. In the absence of expensive oxidants and external supporting electrolyte, the selective oxidation of benzylic C−H bonds in air was achieved.

Abstract

The selective oxidation of benzylic C−H bonds is a pivotal transformation in organic synthesis. Undoubtedly, achieving efficient and highly selective aerobic oxidation of methylarenes to benzaldehydes has been highly challenging due to the propensity of benzaldehyde to undergo overoxidation under typical aerobic conditions. Herein, we propose an innovative approach to address this issue by leveraging electrocatalytic processes, facilitated by ion-pair mediators [Ph₃C]⁺[B(C₆F₅)₄]⁻. By harnessing the power of electrochemistry, we successfully demonstrated the effectiveness of our strategy, which enables the selective oxidation of benzylic C−H bonds in benzylic molecules and toluene derivatives. Notably, our approach exhibited high efficiency, excellent selectivity, and compatibility with various functional groups, underscoring the broad applicability of our methodology.

A formal C(sp²)−H alkylation via the dibenzothiophenylation/nickel-catalyzed eXEC sequence is presented. The first activation step selectively gives aryldibenzothiophenium salts, which are subsequently engaged in electroreductive nickel catalysis. The method provides various C(sp²)−C(sp³) linkages with high sp³-hybridized carbon contents. The demonstration of one-pot alkylations further reinforces the practicality of our approach.

Abstract

Producing sp³-hybridized carbon-enriched molecules is of particular interest due to their high success rate in clinical trials. The installation of aliphatic chains onto aromatic scaffolds was accomplished by nickel-catalyzed C(sp²)−C(sp³) cross-electrophile coupling with arylsulfonium salts. Thus, simple non-prefunctionalized arenes could be alkylated through the formation of aryldibenzothiophenium salts. The reaction employs an electrochemical approach to avoid potentially hazardous chemical redox agents, and importantly, the one-pot alkylation proved also viable, highlighting the robustness of our approach.

A comparison between the recently reported organo-mediator enabled deuteration of styrenes and previously published direct methods display that his transformation does not establish a novel concept, but simply an addition to the portfolio of known reactions. Addition of mediators to our established direct electrolysis protocol and direct conversion of reported scope examples serve further to strengthen this statement.

Abstract

The recently reported electrochemical, organo-mediator enabled deuteration of styrenes, a reaction referred to as “electrochemical deuterium atom transfer”, differs mechanistically from reported direct electrochemical hydrogenations/deuterations only by a mediated, homogeneous SET to the substrates. By comparing direct vs. mediated processes in general and for styrene reduction, we display that Qiu's work does not change the concept of this chemistry. Experiments with mediators and the direct reduction of examples from the reported scope show that even electron-rich substrates can be reduced when our direct protocol, published six months before Qiu's work, is applied.

Recent developments on the use of non-transient non-covalent interactions based on elements of groups 14–17 in organic synthesis and organocatalysis are discussed. While halogen and chalcogen bonding are now clearly established in this area, applications of pnictogen and particularly tetrel bonding are only starting to emerge.

Abstract

The use of noncovalent interactions based on electrophilic halogen, chalcogen, pnictogen, or tetrel centers in organocatalysis has gained noticeable attention. Herein, we provide an overview on the most important developments in the last years with a clear focus on experimental studies and on catalysts which act via such non-transient interactions.

Pulsed electrosynthesis efficiently converts aromatic organoboron reagents to aryl radicals. Mechanistic studies reveal that pulsed electrosynthesis overcomes challenges like radical grafting/passivation, homocoupling, overoxidation, and decomposition. This electro-oxidative method enables straightforward functionalization of aromatic organoboron reagents to form aryl C−P, C−Se, C−Te, and C−S bonds.

Abstract

Aryl radicals play a pivotal role as reactive intermediates in chemical synthesis, commonly arising from aryl halides and aryl diazo compounds. Expanding the repertoire of sources for aryl radical generation to include abundant and stable organoboron reagents would significantly advance radical chemistry and broaden their reactivity profile. While traditional approaches utilize stoichiometric oxidants or photocatalysis to generate aryl radicals from these reagents, electrochemical conditions have been largely underexplored. Through rigorous mechanistic investigations, we identified fundamental challenges hindering aryl radical generation. In addition to the high oxidation potentials of aromatic organoboron compounds, electrode passivation through radical grafting, homocoupling of aryl radicals, and decomposition issues were identified. We demonstrate that pulsed electrosynthesis enables selective and efficient aryl radical generation by mitigating the fundamental challenges. Our discoveries facilitated the development of the first electrochemical conversion of aryl potassium trifluoroborate salts into aryl C−P bonds. This sustainable and straightforward oxidative electrochemical approach exhibited a broad substrate scope, accommodating various heterocycles and aryl chlorides, typical substrates in transition-metal catalyzed cross-coupling reactions. Furthermore, we extended this methodology to form aryl C−Se, C−Te, and C−S bonds, showcasing its versatility and potential in bond formation processes.

The fluorous photoredox catalyst 8R _f8 -4CzIPN (R _f8 =C₈F₁₇) forms a supramolecular complex with chloride ions with high affinity. Integrating fluorous chains on the parent dye greatly enhances both the ion-binding affinity, as well as the oxidizing ability of the catalyst. Efficient photooxidation of the chloride was observed, generating the chlorine HAT reagent, which was tested in the redox-neutral Giese-type C(sp³)−H bond alkylation reaction.

Abstract

The chlorine radical is a strong HAT (Hydrogen Atom Transfer) agent that is very useful for the functionalization of C(sp³)−H bonds. Albeit highly attractive, its generation from the poorly oxidizable chloride ion mediated by an excited photoredox catalyst is a difficult task. We now report that 8R _f8 -4CzIPN, an electron-deficient fluorous derivative of the benchmark 4CzIPN photoredox catalyst belonging to the donor-acceptor carbazole-cyanoarene family, is not only a better photooxidant than 4CzIPN, but also becomes an excellent host for the chloride ion. Combining these two properties ultimately makes the self-assembled 8R _f8 -4CzIPN•Cl⁻ dual catalyst highly reactive in redox-neutral Giese-type C(sp³)−H bond alkylation reactions promoted by the chlorine radical. Additionally, because of its fluorous character, the efficient separation/recovery of 8R _f8 -4CzIPN could be envisioned.

A well-defined iron catalyst with high efficiency for Suzuki–Miyaura coupling involving C(sp³) partners is described. In the presence of a lithium amide base, this catalyst enabled, for the first time, C(sp³)−C(sp²) coupling of 1°, 2°, and 3° alkyl halides and (hetero)aryl boronic esters as well as C(sp³)−C(sp³) coupling of 1° and 2° alkyl halides and 1° and 2° alkyl boranes under mild conditions and with broad functional group tolerance.

Abstract

Despite the paramount importance of the Suzuki–Miyaura coupling (SMC) in academia and industry, and the great promise of iron to offer sustainable catalysis, iron-catalyzed SMC involving sp³-hybridized partners is still in its infancy. We herein report the development of a versatile, well-defined electron-deficient anilido-aldimine iron(II) catalyst. This catalyst effectively performed C(sp³)−C(sp²) and C(sp³)−C(sp³) SMC of alkyl halide electrophiles and (hetero)aryl boronic ester and alkyl borane nucleophiles respectively, in the presence of a lithium amide base. These couplings operated under mild reaction conditions and displayed wide functional group compatibility including various medicinally relevant N-, O- and S-based heterocycles. They also tolerated primary, secondary and tertiary alkyl halides (Br, Cl, I), electron-neutral, -rich and -poor boronic esters and primary and secondary alkyl boranes. Our methodology could be directly and efficiently applied to synthesize key intermediates relevant to pharmaceuticals and a potential drug candidate. For C(sp³)−C(sp²) couplings, radical probe experiments militated in favor of a carbon-centered radical derived from the electrophile. At the same time, reactions run with a pre-formed activated boron nucleophile coupled to competition experiments supported the involvement of neutral, rather than an anionic, (hetero)aryl boronic ester in the key transmetalation step.

A dual nickel/photoredox catalyzed selective radical-radical cross-coupling reaction has been developed with readily available carboxylic acids and their NHPI ester derivatives as coupling partners. This synergistic catalysis enables the mild and efficient building of C(sp²)−C(sp³) bonds or C(sp³)−C(sp³) bonds, affording structurally complex ketones and congested products with all-carbon quaternary centers.

Abstract

Controlling the cross-coupling reaction between two different radicals is a long-standing challenge due to the process occurring statistically, which would lead to three products, including two homocoupling products and one cross-coupling product. Generally, the cross-coupling selectivity is achieved by the persistent radical effect (PRE) that requires the presence of a persistent radical and a transient radical, thus resulting in limited radical precursors. In this paper, a highly selective cross-coupling of alkyl radicals with acyl radicals to construct C(sp²)−C(sp³) bonds, or with alkyl radicals to construct C(sp³)−C(sp³) bonds have been achieved with the readily available carboxylic acids and their derivatives (NHPI ester) as coupling partners. The success originates from the use of tridentate ligand (2,2′ : 6′,2′′-terpyridine) to enable radical cross-coupling process to Ni-mediated organometallic mechanism. This protocol offers a facile and flexible access to structurally diverse ketones (up to 90 % yield), and also a new solution for the challenging double decarboxylative C(sp³)−C(sp³) coupling. The broad utility and functional group tolerance are further illustrated by the late-stage functionalization of natural-occurring carboxylic acids and drugs.

A single terminal [Ni^II−OH] catalyst is employed for direct Julia-type olefination of alcohols and α-alkylation of sulfones using different reaction conditions. Detailed mechanistic studies, including DFT calculations, are undertaken to gain insight on the reaction pathway.

Abstract

A terminal [Ni^II−OH] complex 1, supported by triflamide-functionalized NHC ligands, showed divergent reactivity for the reaction of sulfone with alcohol, contingent on base concentration, temperature, and time. Julia-type olefination of alcohols with sulfones was achieved using one equiv. of base, whereas lowering base loading to 0.5 equiv. afforded α-alkylated sulfones. Besides excellent substrate scope and selectivity, biologically active stilbene derivatives DMU-212, pinosylvin, resveratrol, and piceatannol were synthesized in high yield under Julia-type olefination conditions. An extensive array of controlled experiments and DFT calculations provide valuable insight on the reaction pathway.

Synthetic organic electrochemistry offers sustainable, tunable, and scalable methods for organic synthesis, but optimizing reaction conditions is challenging due to the enlarged dimensionality and complexity of electrochemical reactions. We propose a machine learning approach combining data-driven yield prediction and orthogonal experimental design to efficiently identify optimal conditions for the palladaelectro-catalyzed annulation reaction. This work demonstrates that the synergy between organic electrochemistry and data-driven approaches has the potential to significantly accelerate the development of synthetic electrochemistry.