Nanostructured electrocatalysts for organic synthetic transformations.

Organic chemists have made and are still making enormous efforts toward the development of novel green catalytic synthesis. The necessity arises from the imperative of safeguarding human health and the environment, while ensuring efficient and sustainable chemical production. Within this context, electrocatalysis provides a framework for the design of new organic reactions under mild conditions. Undoubtedly, nanostructured materials are under the spotlight as the most popular and in most cases efficient platforms for advanced organic electrosynthesis. This Minireview focuses on the recent developments in the use of nanostructured electrocatalysts, highlighting the correlation between their chemical structures and resulting catalytic abilities, and pointing to future perspectives for their application in cutting-edge areas.

Synthesis of a novel tetra-phenol π-extended phenazine and its application as an organo-photocatalyst.

In this paper, the synthesis of a novel tetra-phenol π-extended dihydrophenazine is reported. The obtained derivative presents marked reducing properties in the excited state and was exploited as an organo-photocatalyst in dehalogenation and C-C bond formation reactions. These results underline the great potential of functionalized π-extended dihydrophenazines as organo-photocatalysts.

Singlet-Triplet Energy Inversion in Carbon Nitride Photocatalysts.

Time-resolved EPR (TR-EPR) demonstrates the formation of well-defined spin triplet excitons in carbon nitride. This permits to experimentally probe the extent of the triplet wavefunction which delocalizes over several tri-s-triazine units. Analysis of the temperature dependence of the TR-EPR signal reveals the mobility of the triplet excitons. By employing monochromatic light excitation in the range 430-600 nm, the energy of the spin triplet is estimated to be ≈0.2 eV above the conduction band edge, proving that the triplet exciton lies above the corresponding singlet. Comparison between amorphous and graphitic forms establishes the singlet-triplet inversion as a general feature of carbon nitride materials.

Carbon Vacancies Steer the Activity in Dual Ni Carbon Nitride Photocatalysis.

The manipulation of carbon nitride (CN) structures is one main avenue to enhance the activity of CN-based photocatalysts. Increasing the efficiency of photocatalytic heterogeneous materials is a critical step toward the realistic implementation of sustainable schemes for organic synthesis. However, limited knowledge of the structure/activity relationship in relation to subtle structural variations prevents a fully rational design of new photocatalytic materials, limiting practical applications. Here, the CN structure is engineered by means of a microwave treatment, and the structure of the material is shaped around its suitable functionality for Ni dual photocatalysis, with a resulting boosting of the reaction efficiency toward many CX (X = N, S, O) couplings. The combination of advanced characterization techniques and first-principle simulations reveals that this enhanced reactivity is due to the formation of carbon vacancies that evolve into triazole and imine N species able to suitably bind Ni complexes and harness highly efficient dual catalysis. The cost-effective microwave treatment proposed here appears as a versatile and sustainable approach to the design of CN-based photocatalysts for a wide range of industrially relevant organic synthetic reactions.

DoE-Assisted Development of a 2H-MoS2 -Catalyzed Approach for the Production of Indole Derivatives.

2H-MoS2 is an appealing semiconductor because of its Earth-abundant nature, cheapness, and low toxicity. This material has shown promising catalytic activity for various energy-related processes, but its use in catalysis for C-C bond forming reactions towards useful organic compounds is still largely unexplored. The lack of examples in organic synthesis is mainly due to the intrinsic difficulties of using bulk 2H-MoS2 (e. g., low surface area), which implies the reliance on high catalytic loadings for obtaining acceptable yields. This makes the optimization process more expensive and tedious. Here, we report the development of a 2H-MoS2 -mediated synthesis of valuable bis(indolyl)methane derivatives, using indoles and benzaldehydes as starting materials. Exploiting the Design of Experiments (DoE) method, we identified the critical parameters affecting the catalytic performance of commercial 2H-MoS2 powder and optimized the reaction conditions. Lastly, we demonstrated that the catalytic system has versatility and good tolerance towards functional group variations of the reagents.

Graphitic Carbon Nitride as Photocatalyst for the Direct Formylation of Anilines.

The use of graphitic carbon nitride (g-CN) for the photocatalytic radical formylation of anilines, which represents a more sustainable and attractive alternative to the currently used approaches, is reported herein. Our operationally simple method occurs under mild conditions, employing air as an oxidant. In particular, the chemistry is driven by the ability of g-CN to reach an electronically excited state upon visible-light absorption, which has a suitable potential energy to trigger the formation of reactive α-amino radical species from anilines. Mechanistic investigations also proved the key role of the g-CN to form reactive superoxide radicals from O2 via single electron transfer. Importantly, this photocatalytic transformation provides a variety of functionalized formamides (15 examples, up to 89 % yield).

Direct C2-H alkylation of indoles driven by the photochemical activity of halogen-bonded complexes.

A light-driven metal-free protocol for the synthesis of sulfone-containing indoles under mild conditions is reported. Specifically, the process is driven by the photochemical activity of halogen-bonded complexes formed upon complexation of a sacrificial donor, namely 1,4-diazabicyclo[2.2.2]octane (DABCO), with α-iodosulfones. The reaction provides a variety of densely functionalized products in good yields (up to 96% yield). Mechanistic investigations are reported. These studies provide convincing evidences for the photochemical formation of reactive open-shell species.

Photoinduced Cascade Reactions of 2-Allylphenol Derivatives toward the Production of 2,3-Dihydrobenzofurans.

A light-driven protocol for the synthesis of 2,3-dihydrobenzofurans under mild conditions is reported. Specifically, the cascade process is initiated by the photochemical activity of allyl-functionalized phenolate anions, generated in situ upon deprotonation of the corresponding phenols. The reaction proceeds rapidly with reaction times as low as 35 min, delivering a wide range of densely functionalized products (20 examples, yields up to 69%). Mechanistic studies have also been performed providing convincing evidence for the photochemical formation of carbon-centered radical species. A cascade reaction pathway involving a tandem atom transfer radical addition (ATRA) and an intramolecular nucleophilic substitution (SN) process is proposed to occur.

Tailoring the Chemical Structure of Nitrogen-Doped Carbon Dots for Nano-Aminocatalysis in Aqueous Media.

Amine-rich carbon dots (NCDs) have become promising nano-aminocatalytic platforms in organic synthesis. These nanomaterials can be effectively produced through straightforward bottom-up approaches using inexpensive nitrogen-containing molecular precursors as a starting material. However, to date, there is still a limited understanding of how the molecular features of these precursors affect the catalytic activity of the resulting nanoparticles. This study concerns the production of a new family of NCDs, which use l-arginine and different alkyl diamines as starting materials. The surface amines of all these NCDs were comprehensively characterized, thus allowing us to provide a correlation between the structural features of the nanoparticles and their catalytic performance with a selected amino-catalyzed organic transformation. Importantly, the most active nano-aminocatalysts, namely, NCDs-3, were then used as a basis for the formation of a wide variety of functionalized organic compounds in water under mild reaction conditions.

Morphology and Light-Dependent Spatial Distribution of Spin Defects in Carbon Nitride.

Carbon nitride (CN) is a heterogeneous photocatalyst that combines good structural properties and a broad scope. The photocatalytic efficiency of CN is associated with the presence of defective and radical species. An accurate description of defective states-both at a local and extended level-is key to develop a thorough mechanistic understanding of the photophysics of CN. In turn, this will maximise the generation and usage of photogenerated charge carriers and minimise wasteful charge recombination. Here the influence of morphology and light-excitation on the number and chemical nature of radical defects is assessed. By exploiting the magnetic dipole-dipole coupling, the spatial distribution of native radicals in CN is derived with high precision. From the analysis an average distance in the range 1.99-2.34 nm is determined, which corresponds to pairs of radicals located approximately four tri-s-triazine units apart.

Radical defects modulate the photocatalytic response in 2D-graphitic carbon nitride.

Graphitic carbon nitride (gCN) is an important heterogeneous metal-free catalytic material. Thermally induced post-synthetic modifications, such as amorphization and/or reduction, were recently used to enhance the photocatalytic response of these materials for certain classes of organic transformations, with structural defects possibly playing an important role. The knowledge of how these surface modifications modulate the photocatalytic response of gCN is therefore not only interesting from a fundamental point of view, but also necessary for the development and/or tuning of metal-free gCN systems with superior photo-catalytic properties. Herein, employing density functional theory calculations and combining both the periodic and molecular approaches, in conjunction with experimental EPR measurements, we demonstrate that different structural defects on the gCN surface generate distinctive radical defect states localized within the electronic bandgap, with only those correlated with amorphous and reduced gCN structures being photo-active. To this end, we (i) model defective gCN surfaces containing radical defect states; (ii) assess the interactions of these defects with the radical precursors involved in the photo-driven alkylation of electron-rich aromatic compounds (namely perfluoroalkyl iodides); and (iii) describe the photo-chemical processes triggering the initial step of that reaction at the gCN surface. We provide a coherent structure/photo-catalytic property relationship on defective gCN surfaces, elaborating how only specific defect types act as binding sites for the perfluoroalkyl iodide reagent and can favor a photo-induced charge transfer from the gCN surface to the molecule, thus triggering the perfluoroalkylation reaction.

The Nickel Age in Synthetic Dual Photocatalysis: A Bright Trip Toward Materials Science.

Recently, the field of dual photocatalysis has grown rapidly, to become one of the most powerful tools for the functionalization of organic molecules under mild conditions. In particular, the merging of Earth-abundant nickel-based catalytic systems with visible-light-activated photoredox catalysts has allowed the development of a number of unique green synthetic approaches. This goes in the direction of ensuring an effective and sustainable chemical production, while safeguarding human health and environment. Importantly, this relatively new branch of catalysis has inspired an interdisciplinary stream of research that spans from inorganic and organic chemistry to materials science, thus establishing itself as one dominant trend in modern organic synthesis. This Review aims at illustrating the milestones on the timeline evolution of the photocatalytic systems used, with a critical analysis toward novel applications based on the use of photoactive two-dimensional carbon-based nanostructures. Lastly, forward-looking opportunities within this intriguing research field are discussed.

The Photochemical Activity of a Halogen-Bonded Complex Enables the Microfluidic Light-Driven Alkylation of Phenols.

A mild light-driven protocol for the direct alkylation of phenols is reported. The process is driven by the photochemical activity of a halogen-bonded complex formed upon complexation of the in situ generated electron-rich phenolate anion with the α-iodosulfone. The reaction proceeds rapidly (10 min) under microfluidic conditions, delivering a wide variety of ortho-alkylated products (27 examples, up to 97% yield, >20:1 regioselectivity, on a gram scale), including densely functionalized bioactive phenol derivatives.

Amine-Rich Carbon Dots as Novel Nano-Aminocatalytic Platforms in Organic Synthesis.

The development of novel and effective metal-free catalytic systems, which can drive value-added organic transformations in environmentally benign solvents (for instance, water), is highly desirable. Moreover, these new catalysts need to be harmless, easy-to-prepare, and potentially recyclable. In this context, amine-rich carbon dots (CDs) have recently emerged as promising nano-catalytic platforms. These nitrogen-doped nanoparticles, which show dimensions smaller than 10 nm, generally consist of carbon cores that are surrounded by shells containing numerous amino groups. In recent years, organic chemists have used these surface amines to guide the design of several synthetic methodologies under mild operative conditions. This Concept highlights the recent advances in the synthesis of amine-rich carbon dots and their applications in organic catalysis, including forward-looking opportunities within this research field.

Turning the Light on Phenols: New Opportunities in Organic Synthesis.

Phenols (I) are extremely relevant chemical functionalities in natural, synthetic and industrial chemistry. Their corresponding electron-rich anions, namely phenolates (I), are characterized by interesting physicochemical properties that can be drastically altered upon light excitation. Specifically, phenolates (I) become strong reducing agents in the excited state and are able to generate reactive radicals from suitable precursors via single-electron transfer processes. Thus, these species can photochemically trigger strategic bond-forming reactions, including their direct aromatic C-H functionalization. Moreover, substituted phenolate anions can act as photocatalysts to enable synthetically useful organic transformations. An alternative mechanistic manifold is represented by the ability of phenolate derivatives I to form ground state electron donor-acceptor (EDA) complexes with electron-poor radical sources. These complementary scenarios have paved the way for the development of a wide range of relevant organic reactions. In this Minireview, we present the main examples of this research field, and give insight on emerging trends in phenols photocatalysis towards richer organic synthesis.

Metal-Free Photocatalysis: Two-Dimensional Nanomaterial Connection toward Advanced Organic Synthesis.

Two-dimensional (2D) nanostructures are a frontier in materials chemistry as a result of their extraordinary properties. Metal-free 2D nanomaterials possess extra appeal due to their improved cost-effectiveness and lower toxicity with respect to many inorganic structures. The outstanding electronic characteristics of some metal-free 2D semiconductors have projected them into the world of organic synthesis, where they can function as high-performance photocatalysts to drive the sustainable synthesis of high-value organic molecules. Recent reports on this topic have inspired a stream of research and opened up a theme that we believe will become one of the most dominant trends in the forthcoming years.

Light-driven, heterogeneous organocatalysts for C-C bond formation toward valuable perfluoroalkylated intermediates.

The favorable exploitation of carbon nitride (CN) materials in photocatalysis for organic synthesis requires the appropriate fine-tuning of the CN structure. Here, we present a deep investigation of the structure/activity relationship of CN in the photocatalytic perfluoroalkylation of organic compounds. Four types of CN bearing subtle structural differences were studied via conventional characterization techniques and innovative nuclear magnetic resonance (NMR) experiments, correlating the different structures with the fundamental mechanistic nexus and especially highlighting the importance of the halogen bond strength between the reagent and the catalyst surface. The optimum catalyst exhibited an excellent performance, with a very wide reaction scope, and could prominently trigger the model reaction using natural sunlight. The work lays a platform for establishing a new approach in the development of heterogeneous photocatalysts for organic synthesis related to medical, agricultural, and material chemistry.

Novel idebenone analogs block Shc's access to insulin receptor to improve insulin sensitivity.

There has been little innovation in identifying novel insulin sensitizers. Metformin, developed in the 1920s, is still used first for most Type 2 diabetes patients. Mice with genetic reduction of p52Shc protein have improved insulin sensitivity and glucose tolerance. By high-throughput screening, idebenone was isolated as the first small molecule 'Shc Blocker'. Idebenone blocks p52Shc's access to Insulin Receptor to increase insulin sensitivity. In this work the avidity of 34 novel idebenone analogs and 3 metabolites to bind p52Shc, and to block the interaction of p52Shc with the Insulin receptor was tested. Our hypothesis was that if an idebenone analog bound and blocked p52Shc's access to insulin receptor better than idebenone, it should be a more effective insulin sensitizing agent than idebenone itself. Of 34 analogs tested, only 2 both bound p52Shc more tightly and/or blocked the p52Shc-Insulin Receptor interaction more effectively than idebenone. Of those 2 only idebenone analog #11 was a superior insulin sensitizer to idebenone. Also, the long-lasting insulin-sensitizing potency of idebenone in rodents over many hours had been puzzling, as the parent molecule degrades to metabolites within 1 h. We observed that two of the idebenone's three metabolites are insulin sensitizing almost as potently as idebenone itself, explaining the persistent insulin sensitization of this rapidly metabolized molecule. These results help to identify key SAR = structure-activity relationship requirements for more potent small molecule Shc inhibitors as Shc-targeted insulin sensitizers for type 2 diabetes.

Synthesis and applications of amino-functionalized carbon nanomaterials.

Carbon-based nanomaterials (CNMs) have attracted considerable attention in the scientific community both from a scientific and an industrial point of view. Fullerenes, carbon nanotubes (CNTs), graphene and carbon dots (CDs) are the most popular forms and continue to be widely studied. However, the general poor solubility of many of these materials in most common solvents and their strong tendency to aggregate remains a major obstacle in practical applications. To solve these problems, organic chemistry offers formidable help, through the exploitation of tailored approaches, especially when aiming at the integration of nanostructures in biological systems. According to our experience with carbon-based nanostructures, the introduction of amino groups is one of the best trade-offs for the preparation of functionalized nanomaterials. Indeed, amino groups are well-known for enhancing the dispersion, solubilization, and processability of materials, in particular of CNMs. Amino groups are characterized by basicity, nucleophilicity, and formation of hydrogen or halogen bonding. All these features unlock new strategies for the interaction between nanomaterials and other molecules. This integration can occur either through covalent bonds (e.g., via amide coupling) or in a supramolecular fashion. In the present Feature Article, the attention will be focused through selected examples of our approach to the synthetic pathways necessary for the introduction of amino groups in CNMs and the subsequent preparation of highly engineered ad hoc nanostructures for practical applications.

Use of Nitrogen-Doped Carbon Nanodots for the Photocatalytic Fluoroalkylation of Organic Compounds.

The use of amine-rich N-doped carbon nanodots (NCNDs) for the photochemical radical perfluoroalkylation of organic compounds is reported. This operationally simple approach occurs under mild conditions producing valuable new C-C bonds. The chemistry is driven by the ability of NCNDs to directly reach an electronically excited state upon light absorption, thereby successively triggering the formation of reactive radical species from simple perfluoroalkyl iodides. Preliminary mechanistic studies are also reported.