Red-light-mediated copper-catalyzed photoredox catalysis promotes regioselectivity switch in the difunctionalization of alkenes.

Controlling regioselectivity during difunctionalization of alkenes remains a significant challenge, particularly when the installation of both functional groups involves radical processes. In this aspect, methodologies to install trifluoromethane (-CF3) via difunctionalization have been explored, due to the importance of this moiety in the pharmaceutical sectors; however, these existing reports are limited, most of which affording only the corresponding ß-trifluoromethylated products. The main reason for this limitation arises from the fact that -CF3 group served as an initiator in those reactions and predominantly preferred to be installed at the terminal (ß) position of an alkene. On the contrary, functionalization of the -CF3 group at the internal (α) position of alkenes would provide valuable products, but a meticulous approach is necessary to win this regioselectivity switch. Intrigued by this challenge, we here develop an efficient and regioselective strategy where the -CF3 group is installed at the α-position of an alkene. Molecular complexity is achieved via the simultaneous insertion of a sulfonyl fragment (-SO2R) at the ß-position. A precisely regulated sequence of radical generation using red light-mediated photocatalysis facilitates this regioselective switch from the terminal (ß) position to the internal (α) position. Furthermore, this approach demonstrates broad substrate scope and industrial potential for the synthesis of pharmaceuticals under mild reaction conditions.

Challenges and recent advancements in the synthesis of α,α-disubstituted α-amino acids.

α,α-Disubstituted α-amino acids (α-AAs) have improved properties compared to other types of amino acids. They serve as modifiers of peptide conformation and as precursors of bioactive compounds. Therefore, it has been a long-standing goal to construct this highly valuable scaffold efficiently in organic synthesis and drug discovery. However, access to α,α-disubstituted α-AAs is highly challenging and largely unexplored due to their steric constraints. To overcome these, remarkable advances have been made in the last decades. Emerging strategies such as synergistic enantioselective catalysis, visible-light-mediated photocatalysis, metal-free methodologies and CO2 fixation offer new avenues to access the challenging synthesis of α,α-disubstituted α-AAs and continuously bring additional contributions to this field. This review article aims to provide an overview of the recent advancements since 2015 and discuss existing challenges for the synthesis of α,α-disubstituted α-AAs and their derivatives.

Photochemical Upcycling/Modification of Polystyrene-based Plastic Waste.

The escalating accumulation of plastic waste in landfills and marine environments has become a pressing concern to society. Among all plastic-based waste, polystyrenes are widely utilized as a commodity plastic and present very low recyclability. To improve this scenario, photocatalysis has recently become one of the viable techniques which can be performed under mild conditions. In this concise review, we have highlighted recent advancements in the valorization of polystyrene-based plastic waste by mainly focusing on the selective functionalization of the C-H bonds. This strategy clearly holds strong promise for the sustainable and efficient conversion of polystyrene-based waste and contributes to the reduction of waste and resource conservation.

Straightforward synthesis of functionalized γ-Lactams using impure CO2 stream as the carbon source.

Direct utilization of CO2 into organic synthesis finds enormous applications to synthesize pharmaceuticals and fine chemicals. However, pure CO2 gas is essential to achieve these transformations, and the purification of CO2 is highly cost and energy intensive. Considering this, we describe a straightforward synthetic route for the synthesis of γ-lactams, a pivotal core structure of bioactive molecules, by using commercially available starting materials (alkenes and amines) and impure CO2 stream (exhaust gas is collected from the car) as the carbon source. This blueprint features a broad scope, excellent functional group compatibility and application to the late-stage transformation of existing pharmaceuticals and natural products to synthesize functionalized γ-lactams. We believe that our strategy will provide direct access to γ-lactams in a very sustainable way and will also enhance the Carbon Capture and Utilization (CCU) strategy.

Visible-light-induced [3+2] cycloadditions of donor/donor diazo intermediates with alkenes to achieve (spiro)-pyrazolines and pyrazoles.

To date, [3 + 2] cycloadditions of diazo esters with alkynes or alkenes have been a robust tool to generate pyrazoles and pyrazolines. However, methods capable of generating donor/donor diazo species from readily available N-tosylhydrazones to furnish [3 + 2] cycloadditions, remain elusive. Herein, we describe the first visible-light-induced [3 + 2] cycloadditions of donor/donor diazo precursors with alkenes to afford pyrazoles and novel (spiro)pyrazolines bearing a quaternary center. This protocol shows a tolerable substrate scope covering versatile carbonyl compounds and alkenes. Late-stage functionalization of bioactive molecules, one-pot approach, and gram-scale synthesis have also been introduced successfully to prove the practicability. At last, mechanistic experiments and DFT studies suggested the formation of non-covalent interactions enabling the activation of N-tosylhydrazones and the formation of the donor/donor diazo intermediates.

An Atomically Dispersed Mn-Photocatalyst for Generating Hydrogen Peroxide from Seawater via the Water Oxidation Reaction (WOR).

In this work, we have fabricated an aryl amino-substituted graphitic carbon nitride (g-C3N4) catalyst with atomically dispersed Mn capable of generating hydrogen peroxide (H2O2) directly from seawater. This new catalyst exhibited excellent reactivity, obtaining up to 2230 µM H2O2 in 7 h from alkaline water and up to 1800 µM from seawater under identical conditions. More importantly, the catalyst was quickly recovered for subsequent reuse without appreciable loss in performance. Interestingly, unlike the usual two-electron oxygen reduction reaction pathway, the generation of H2O2 was through a less common two-electron water oxidation reaction (WOR) process in which both the direct and indirect WOR processes occurred; namely, photoinduced h+ directly oxidized H2O to H2O2 via a one-step 2e- WOR, and photoinduced h+ first oxidized a hydroxide (OH-) ion to generate a hydroxy radical (•OH), and H2O2 was formed indirectly by the combination of two •OH. We have characterized the material, at the catalytic sites, at the atomic level using electron paramagnetic resonance, X-ray absorption near edge structure, extended X-ray absorption fine structure, high-resolution transmission electron microscopy, X-ray photoelectron spectroscopy, magic-angle spinning solid-state NMR spectroscopy, and multiscale molecular modeling, combining classical reactive molecular dynamics simulations and quantum chemistry calculations.

Versatile CO2 Hydrogenation-Dehydrogenation Catalysis with a Ru-PNP/Ionic Liquid System.

High catalytic activities of Ru-PNP [Ru = ruthenium; PNP = bis alkyl- or aryl ethylphosphinoamine complexes in ionic liquids (ILs) were obtained for the reversible hydrogenation of CO2 and dehydrogenation of formic acid (FA) under exceedingly mild conditions and without sacrificial additives. The novel catalytic system relies on the synergic combination of Ru-PNP and IL and proceeds with CO2 hydrogenation already at 25 °C under a continuous flow of 1 bar of CO2/H2 (1:5), leading to 14 mol % FA with respect to the IL. A pressure of 40 bar of CO2/H2 (1:1) provides 126 mol % of FA/IL corresponding to a space-time yield (STY) of FA of 0.15 mol L-1 h-1. The conversion of CO2 contained in imitated biogas was also achieved at 25 °C. Furthermore, the Ru-PNP/IL system catalyzes FA dehydrogenation with average turnover frequencies up to 11,000 h-1 under heat-integrated conditions for proton-exchange membrane fuel cell applications (<100 °C). Thus, 4 mL of a 0.005 M Ru-PNP/IL system converted 14.5 L FA over 4 months with a turnover number exceeding 18,000,000 and a STY of CO2 and H2 of 35.7 mol L-1 h-1. Finally, 13 hydrogenation/dehydrogenation cycles were achieved with no sign of deactivation. These results demonstrate the potential of the Ru-PNP/IL system to serve as a FA/CO2 battery, a H2 releaser, and a hydrogenative CO2 converter.

Π-Π Stacking Complex Induces Three-Component Coupling Reactions To Synthesize Functionalized Amines.

π-π stacking and ion-pairing interactions induced the generation of α-amino radicals under the irradiation of visible light without the requirement of an expensive photocatalyst. This strategy enabled the construction of functionalized amines via three-component coupling reactions with broad scope (we report >50 examples with an up to 90 % yield). This synthetic pathway also delivered complex functionalized amines with a very high yield. Quantum chemistry Density Functional Theory (DFT) calculations identified π-π stacked ionic complexes; time-dependent DFT was employed to simulate the absorption spectra, and nudged elastic band (NEB) methodology provided a possible interaction/reaction picture of the selected species.

Challenges and recent advancements in the transformation of CO2 into carboxylic acids: straightforward assembly with homogeneous 3d metals.

The transformation of carbon dioxide (CO2) into useful chemicals, advanced materials, and energy is a long-standing challenge in both fundamental science and industry. In recent years, utilization of CO2 in the presence of inexpensive and non-negligible environmentally friendly 3d metal-based catalysts (Fe, Mn, Co, Ni, Cu and Ti) has become one of the most attractive topics. Particular attention has been given to the synthesis of carboxylic acids and their derivatives since these molecules serve as key intermediates in the chemical, fertilizer, and pharmaceutical sectors. Considering numerous challenges linked with CO2 reactivity, a number of research groups have recently focused on the transformation of CO2 into carboxylic acids by following thermo-, photo-, and electrochemical strategies. However, facile access to such acids remains a vital challenge in catalysis and in organic synthesis owing to the high stability of the CO2 molecule in which the carbon atom has the highest oxidation state. Another hurdle is to solve the selectivity issue caused by the reaction of different catalytic systems with CO2 in the presence of reactive functional group-containing molecules. Despite all these issues, a wide range of transition metal-based catalysts have been applied in this direction, but owing to their cheaper price and inherent reactivity, 3d metals are at the forefront in the CO2 utilization domain. Considering these, we aim to summarise recent advances (over the past five years) of 3d-metal complexes and their reactivity towards the activation of CO2 for the synthesis of carboxylic acids. Furthermore, we discuss current research trends, knowledge gaps, and invigorating perspectives on future advances.

Transition metal-free approach for late-stage benzylic C(sp3)-H etherifications and esterifications.

We report a transition metal-free approach for the regioselective functionalization of benzylic C(sp3)-H bonds using alcohols and carboxylic acids as the nucleophiles. This straightforward and general route has provided various benzylic ethers and esters, including twelve pharmaceutically relevant compounds.

Lignin-Supported Heterogeneous Photocatalyst for the Direct Generation of H2O2 from Seawater.

The development of smart and sustainable photocatalysts is in high priority for the synthesis of H2O2 because the global demand for H2O2 is sharply rising. Currently, the global market share for H2O2 is around 4 billion US$ and is expected to grow by about 5.2 billion US$ by 2026. Traditional synthesis of H2O2 via the anthraquinone method is associated with the generation of substantial chemical waste as well as the requirement of a high energy input. In this respect, the oxidative transformation of pure water is a sustainable solution to meet the global demand. In fact, several photocatalysts have been developed to achieve this chemistry. However, 97% of the water on our planet is seawater, and it contains 3.0-5.0% of salts. The presence of salts in water deactivates the existing photocatalysts, and therefore, the existing photocatalysts have rarely shown reactivity toward seawater. Considering this, a sustainable heterogeneous photocatalyst, derived from hydrolysis lignin, has been developed, showing an excellent reactivity toward generating H2O2 directly from seawater under air. In fact, in the presence of this catalyst, we have been able to achieve 4085 µM of H2O2. Expediently, the catalyst has shown longer durability and can be recycled more than five times to generate H2O2 from seawater. Finally, full characterizations of this smart photocatalyst and a detailed mechanism have been proposed on the basis of the experimental evidence and multiscale/level calculations.

Transition Metal-Free Synthesis of Carbamates Using CO2 as the Carbon Source.

Utilization of carbon dioxide as a C1 synthon is highly attractive for the synthesis of valuable chemicals. However, activation of CO2 is highly challenging, owing to its thermodynamic stability and kinetic inertness. With this in mind, several strategies have been developed for the generation of carbon-heteroatom bonds. Among these, formation of C-N bonds is highly attractive, especially, when carbamates can be synthesized directly from CO2 . This Minireview focuses on transition metal-free approaches for the fixation of CO2 to generate carbamates for the production of fine chemicals and pharmaceuticals. Within the past decade, transition metal-free approaches have gained increasing attention, but traditional reviews have rarely focused on these approaches. Direct comparisons between such methods have been even more scarce. This Minireview seeks to address this discrepancy.

Metal-free photocatalysts for the oxidation of non-activated alcohols and the oxygenation of tertiary amines performed in air or oxygen.

This protocol describes the use of 9-fluorenone as a cheap and non-toxic photocatalyst for the oxidation of non-activated alcohols performed under the irradiation of a blue light-emitting diode. It also describes the use of the similarly cheap and non-toxic photocatalyst rose bengal for the selective α-oxygenation of tertiary amines to produce the corresponding amides in a selective way using the same light source. We have provided detailed instructions on how to assemble the light-emitting diode equipment and set up the photocatalytic reaction, where an oxygen atmosphere is created with an O2-filled balloon. Further details are provided using four example reactions that illustrate how this system works: alcohol oxidation to prepare terephthlalaldehyde and androstanedione, and amine oxidation to make 2-phenyl-3,4-dihydroisoquinolin-1(2H)-one and (4-((4-chlorophenyl)(phenyl)methyl)piperazin-1-yl)m-tolyl)methanone. The times needed to perform these photocatalytic reactions are 18, 76, 22 and 54 h, respectively. We believe that this protocol represents a robust methodology for the late-stage modification of amines and the selective oxidation of steroids.

Visible-Light-Mediated Dearomatisation of Indoles and Pyrroles to Pharmaceuticals and Pesticides.

Dearomatisation of indole derivatives to the corresponding isatin derivatives has been achieved with the aid of visible light and oxygen. It should be noted that isatin derivatives are highly important for the synthesis of pharmaceuticals and bioactive compounds. Notably, this chemistry works excellently with N-protected and protection-free indoles. Additionally, this methodology can also be applied to dearomatise pyrrole derivatives to generate cyclic imides in a single step. Later this methodology was applied for the synthesis of four pharmaceuticals and a pesticide called dianthalexin B. Detailed mechanistic studies revealed the actual role of oxygen and photocatalyst.

Metal-Free Photocatalysts for C-H Bond Oxygenation Reactions with Oxygen as the Oxidant.

Direct and selective oxygenation of C-H bonds to C-O bonds is regarded as an effective tool to generate high-value products. However, these reactions are still subject to challenges such as harsh reaction conditions, use of expensive transition metal catalysts, and involvement of stoichiometric oxidants. To avoid these, molecular oxygen would be ideal as oxidant, as the byproduct is water or hydrogen peroxide. Additionally, achieving these reactions by using metal-free catalysts would contribute to green and sustainable chemical synthesis. This Minireview summarizes recent reports on C-H oxygenation reactions with metal-free catalysts and molecular oxygen under visible-light conditions.

Delineating the Mechanism of Ionic Liquids in the Synthesis of Quinazoline-2,4(1H,3H)-dione from 2-Aminobenzonitrile and CO2.

Ionic liquids (ILs) are versatile solvents and catalysts for the synthesis of quinazoline-2,4-dione from 2-aminobenzonitrile and CO2 . However, the role of the IL in this reaction is poorly understood. Consequently, we investigated this reaction and showed that the IL cation does not play a significant role in the activation of the substrates, and instead plays a secondary role in controlling the physical properties of the IL. A linear relationship between the pKa of the IL anion (conjugate acid) and the reaction rate was identified with maximum catalyst efficiency observed at a pKa of >14.7 in DMSO. The base-catalyzed reaction is limited by the acidity of the quinazoline-2,4-dione product, which is deprotonated by more basic catalysts, leading to the formation of the quinazolide anion (conjugate acid pKa 14.7). Neutralization of the original catalyst and formation of the quinazolide anion catalyst leads to the observed reaction limit.

N-formylation and N-methylation of amines using metal-free N-heterocyclic carbene catalysts and CO2 as carbon source.

N-formylation and N-methylation of amines are important reactions that are used to produce a wide range of key intermediates and compounds. This protocol describes the environmentally benign N-formylation and N-methylation of primary and secondary amines using carbon dioxide (CO2) as the carbon source, hydrosilanes as reductants and N-heterocyclic carbenes (NHCs) as catalysts. Using CO2 as a reagent has the advantage of low cost and negligible toxicity. However, the catalyst is air-sensitive and must be generated fresh before use; consequently, the techniques used to prepare and manipulate the catalyst are described. The synthetic approach described in this protocol does not use any toxic reagents; using the appropriate catalyst, N-formylated or N-methylated products can be obtained with high selectivity. The overall time for catalyst preparation and for conducting several catalytic reactions in parallel is 15-48 h, depending on the nature of the substrates.

Synthesis of cyclic carbonates from diols and CO2 catalyzed by carbenes.

The synthesis of cyclic carbonates from epoxides and CO2 is a well-established reaction, whereas the synthesis of cyclic carbonates from diols and CO2 is considerably more challenging, and few efficient catalysts are available. Here, we describe heterocyclic carbene catalysts, including one derived from a cheap and efficient thiazolium salt, for this latter reaction. The reaction proceeds at atmospheric pressure in the presence of an alkyl halide and Cs2CO3. Reaction mechanisms for the transformations involved are also proposed.

Chemoselective Synthesis of Carbamates using CO2 as Carbon Source.

Synthesis of carbamates directly from amines using CO2 as the carbon source is a straightforward and sustainable approach. Herein, we describe a highly effective and chemoselective methodology for the synthesis of carbamates at room temperature and atmospheric pressure. This methodology can also be applied to protect the amino group in amino acids and peptides, and also to synthesize important pharmaceuticals.

A General and Selective Rhodium-Catalyzed Reduction of Amides, N-Acyl Amino Esters, and Dipeptides Using Phenylsilane.

This article describes a selective reduction of functionalized amides, including N-acyl amino esters and dipeptides, to the corresponding amines using simple [Rh(acac)(cod)]. The catalyst shows excellent chemoselectivity in the presence of different sensitive functional moieties.