Photoinduced Decarboxylation Research Articles

Visible-light-induced decarboxylative radical polymerization in two-molecule photoredox system

Radical polymerization via the photoinduced decarboxylation of carboxylic acids was achieved in a two-molecule photoredox system using visible light. In this photoreaction, unique polymers with chain ends derived from amino acids, peptides, sugars, and steroids were obtained under mild conditions. In addition, a two-molecule photoredox system for replacing both electron donor and acceptor, led to selective decarboxylation, facilitating the preparation of block copolymers with different segments.

The iron(III) coordinating properties of citrate and α-hydroxycarboxylate containing siderophores.

The iron(III) binding properties of citrate and rhizoferrin, a citrate containing siderophore, are compared. Citrate forms many oligonuclear complexes, whereas rhizoferrin forms a single mononuclear complex. The α-hydroxycarboxylate functional group, which is present in both citrate, and rhizoferrin, has a high affinity and selectivity for iron(III) under most biological conditions. The nature of the toxic form of iron found in the blood of patients suffering from many haemoglobinopathies and haemochromatosis is identified as a mixture of iron(III)citrate complexes. The significance of the presence of this iron pool to patients suffering from systemic iron overload is discussed. The wide utilisation of the α-hydroxycarboxylate functional group in siderophore structures is described, as is their photo-induced decarboxylation leading to the release of iron(II) ions. The importance of this facile dissociation to algal iron uptake is discussed.

Coumarin based glyoxylate photoinitiators for free radical and cationic Photopolymerizations with UV-Visible LED irradiation

High-performance photoinitiators (PIs) play a crucial role in ultraviolet–visible (UV–Vis) photopolymerization. In this study, three coumarin-3-oxoacetic acid methyl esters (COAEs) which demonstrate significant UV–Vis absorption within the 300–500 nm range were synthesized and studied. Real-time fourier transform infrared (RT-FTIR) and photo-differential scanning calorimetry (photo-DSC) experiments demonstrated that these PIs can function as Type I and Type II PIs for initiating free radical polymerization (FRP) of acrylate monomers. Additionally, they can serve as photosensitizers for iodonium salts and sulfonium salts, enabling cationic photopolymerization (CP) of epoxy and oxetane monomers. Remarkably, even at low concentrations of 0.01 wt%, they can effectively initiate the deep curing of Tri-(propylene glycol) diacrylate (TPGDA) to a depth of approximately 9 cm after 5 min of irradiation with a 415 nm or 450 nm LED light source. Furthermore, the COAEs exhibit satisfactory photobleaching properties, making them suitable for colorless applications in photopolymerization. The photochemical and photophysical properties of the COAEs were thoroughly investigated using absorption spectroscopy, electron spin resonance, cyclic voltammetry experiments, and photoinduced decarboxylation experiments to elucidate the photoinitiation mechanism. Cytotoxicity experiments revealed that COAE-N exhibited good cytocompatibility. Therefore, the exceptional polymerization properties of COAEs offer promising prospects for FRP and CP applications. Additionally, their efficient photobleaching characteristics make them highly suitable for deep photopolymerization applications. Moreover, the low cytotoxicity of COAEs suggests significant potential for biomedical applications such as dental restoration.

UV irradiation induced simultaneous reduction of Cu(II) and degradation of EDTA in Cu(II)-EDTA in wastewater containing Cu(II)-EDTA

Decomplexation of Cu(II)-EDTA followed by chemical precipitation of free Cu(II) ions can effectively degrade EDTA in Cu(II)-EDTA and remove Cu(II), but requires large precipitant dosage and inevitably produces a large amount of copper-containing sludge that is difficult to deal with. Herein, we demonstrated that simultaneous reduction of Cu(II) and degradation of EDTA in Cu(II)-EDTA can be achieved by UV irradiation of wastewater containing Cu(II)-EDTA without adding reagent. 93.65% of Cu(II) was reduced to Cu(0) with a high purity of 99.93 wt%, which can be recycled, thus avoiding the generation of copper-containing sludge. 96.67% of EDTA in Cu(II)-EDTA was degraded, and the final products were HCHO, NH4+, NO3- and low-molecular acids. In depth, the dominant degradation mechanism of EDTA in Cu(II)-EDTA was photo-induced successive decarboxylation through homolysis of C-O and C-C bond of -CH2-COOH group, followed by ligand to metal charge transfer (LMCT) and hydrolysis reactions. The minor degradation mechanism of EDTA in Cu(II)-EDTA was successive decarboxylation by •OH radicals. Simultaneously, Cu(II) was reduced to Cu(0) by H• and eaq- produced by UV irradiation of Cu(II)-EDTA. This study provided an approach of simultaneous removal of heavy metals and degradation of EDTA in Cu(II)-EDTA in wastewater containing heavy metal-EDTA complex.

Diastereoselective Hydroacylation of Cyclopropenes by Visible-Light Photocatalysis.

An efficient and general strategy for the hydroacylation of cyclopropene is disclosed for synthesizing various 2-acylcyclopropane derivatives under mild reaction conditions. High functional group tolerance of this protocol features a novel route to access a divergent synthesis of acylated cyclopropane in a diastereoselective manner by photoinduced decarboxylation of α-ketoacid followed by acyl radical addition to cyclopropene. Additionally, the regioselective addition of acyl radical at the least substituted olefinic carbon center with trans-selective fashion makes this protocol more appealing toward natural product development.

Visible-Light-Mediated Three-Component Decarboxylative Coupling Reactions to Synthesize 1,4-Diol Monoethers.

An efficient approach for 1,2-difunctionalization of aromatic olefins and the synthesis of functionalized 1,4-diols monoethers has been established via a photoinduced three-component reaction of an α-alkoxycarboxylic acid, an aromatic olefin, and an aldehyde. The reaction proceeds by photoinduced oxidative decarboxylation of the carboxylic acid followed by the addition of the α-alkoxyalkyl radical to the olefin, one-electron reduction of the addition radical, and the nucleophilic attack of the resulting carbanion to the aldehyde. Besides the convenient one-pot protocol of the three-component reaction, this method offers several other advantages, including good functional group tolerance for the three substrates, gentle reaction conditions, and ease of scaling up. The reaction mechanism has been investigated through free radical trapping experiment and isotope labeling experiments.

Photoredox/nickel cooperatively catalyzed radical allylic silylation of allyl acetates – Scope and mechanism

The compatibility between photogenerated silyl radicals and transition metal catalysis remains one of the foremost challenges in modern synthetic organic chemistry. Herein, we present the cooperation of photoredox/nickel catalyzed allylic silylation of diverse allyl acetates (even with multiple alkenyl groups) via a silyl radical intermediate. This protocol successfully surmounts the long-standing challenge and provides straightforward, modular synthetic access to substituted allylsilanes from silanecarboxylic acids. Moreover, this strategy has advantages of green and mild conditions over established nucleophilic substitution methods via a silanion pathway. Mechanistic study shows that the formation of silyl radical initiated by photo-induced decarboxylation of silanecarboxylic acids, and the nickel-catalyzed oxidative addition of allyl acetate, followed by silyl radical addition are critical processes. DFT computation reveals that the regioselectivity is controlled by the silyl radical attack of the sterically less hindered or less substituted terminal allylic carbon atom.

Merging Photoinduced Iron-Catalyzed Decarboxylation with Copper Catalysis for C–N and C–C Couplings

We report a photoinduced iron/copper dual-catalytic strategy for the radical decarboxylation functionalization of aliphatic carboxylic acids. The photoinduced ligand-to-iron charge transfer process under light was initially occurred to generate an unstabilized alkyl radical, and the copper catalyst delivered the radical and enabled the subsequent coupling reactions to form C–N or C–C bonds. By merging iron-catalyzed decarboxylation with copper catalysis, this system allows the smooth conversion of a wide range of aliphatic carboxylic acids for the amination, decarboxylative dehydrogenation, and alkylation efficiently. A wide variety of complex drug or natural molecules is applicable, suggesting that this strategy would facilitate rapid compound library synthesis and benefit to the discovery of pharmaceutical agents.

Visible‐Light‐Induced Decarboxylative and Deboronative Radical Addition to Alkenes in Two‐Molecule Photoredox System Using Dibenzo[g,p]chrysene

AbstractVisible‐light‐induced decarboxylative and deboronative radical addition of aliphatic carboxylic acids and arylboronic acid pinacol esters to electron‐deficient alkenes using two‐molecule organic photoredox catalysts, such as dibenzo[g,p]chrysene as an electron donor and 1,4‐dicyanobenzene as an electron acceptor, proceeded efficiently to furnish radical adducts via the generation of alkyl and aryl radicals. The base and substrate play important roles in this photochemical system, and the sequential photoinduced decarboxylation of glutamic acid having two different carboxy groups was successful.

Functionalization of Aspartic or Glutamic Acids through Photoinduced Decarboxylation

Key words aspartic acid - glutamic acid - photoredox catalysis - late-stage modification - alkenes - decarboxylation

Decarboxylative Side-Chain Functionalization of Aspartic/Glutamic Acids Using Two-Molecule Photoredox Catalysts.

The side-chain functionalization of aspartic/glutamic acid derivatives through photoinduced decarboxylation was achieved by using organic two-molecule photoredox catalysts without racemization under mild conditions. A facile process involving the preparation of substrates and photoinduced decarboxylative radical additions can provide easy access to the linked amino acids with carbohydrates and amino acids at the side chain.

Computational Studies of the Photodegradation Mechanism of the Highly Phototoxic Agent Benoxaprofen.

Computational quantum chemistry within the density functional theory (DFT) and time-dependent density functional theory (TD-DFT) framework is used to investigate the photodegradation mechanism as well as the photochemical and photophysical properties of benoxaprofen (BP), a non steroid anti-inflammatory molecule (2-[2-(4-chlorophenyl)-1,3-benzoxazol-5-yl] propanoic acid). BP is a highly phototoxic agent that causes cutaneous phototoxicity shortly after its administration. On the grounds of concern about serious side effects, especially hepatotoxicity, it was withdrawn from the world market after only 2 years of its release. Our study shows that the drug has the capability to absorb radiation in the UV region, mainly between 300 and 340 nm, and undergoes spontaneous photoinduced decarboxylation from the triplet state. It shows very similar photochemical properties to the highly photolabile non-steroidal anti-inflammatory drugs (NSAIDs) ketoprofen, suprofen, and tiaprofenic acid. Like ketoprofen, BP can also decarboxylate from excited singlet states by overcoming low energy barriers. The differences in molecular orbital (highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO)) distributions between the neutral and deprotonated BP, their absorption spectra, and the energetics and fate of various photoproducts produced throughout the photodegradation are discussed. Initiation and termination of decarboxylated BP radical species and initiation of propagating lipid peroxidation reactions due to the addition of molecular oxygen giving rise to the corresponding peroxyl radical are also explored in detail.

Site-Selective Functionalization of Carboranes at the Electron-Rich Boron Vertex: Photocatalytic B-C Coupling via a Carboranyl Cage Radical.

Functionalization of carboranes in a vertex-specific manner is a perennial challenge. Here, we report a photocatalytic B-C coupling for the selective functionalization of carboranes at the boron site which is most distal to carbon. This reaction was achieved by the photo-induced decarboxylation of carborane carboxylic acids to generate boron vertex-centered carboranyl radicals. Theoretical calculations also demonstrate that the reaction more easily occurs at the boron site bearing higher electron density owing to the lower energy barrier for a single-electron transfer to generate a carboranyl radical. By using this strategy, a number of functionalized carboranes could be accessed through alkylation, alkenylation, and heteroarylation under mild conditions. Moreover, both a highly efficient blue emitter with a solid-state luminous efficiency of 42 % and a drug candidate for boron neutron capture therapy (BNCT) containing targeting and fluorine units were obtained.

Probing the dynamics of the photo-induced decarboxylation of neutral and ionic pyruvic acid.

The dynamics of the electronically excited pyruvic acid (PA) and of its unimolecular decomposition upon single photon ionisation are investigated by means of a table top fs laser and VUV synchrotron radiation. The latter is coupled with photo-ion/photo-electron coincidence acquisition devices that allow the identification of the ionic products coming from state-to-state fragmentation upon ionisation. The fs-based setup provides time-resolved mass spectra with 266 nm (= 4.661 eV) excitation and an 800 nm multiphoton probe. For interpretation, we carried out theoretical computations using a composite scheme combining density functional theory full molecular geometric optimisation and post-Hartree-Fock correction inclusion. We therefore determined the neutral and ionic species formed during these experiments and the corresponding dissociation channels. Although several PA isomers are found, we show that solely the most stable isomer of PA (i.e. Tc) is present in the molecular beam prior to ionisation. We determined its adiabatic ionisation energy (AIE = 10.031 ± 0.005 eV). The fragmentation of the Tc+ ion occurs at ∼0.4 eV above the threshold and it is dominated by the CC bond breaking channel, forming the HOCO fragment in conjunction with the CH3CO+ ion. The decarboxylation of Tc+ channels has a minor contribution, although they are more favourable thermodynamically. These findings are in contrast with the dominance of decarboxylation while fragmenting Tc populated in the S1-S3 states. For explanation, we invoke an indirect process populating first a short lived autoionising neutral state located in energy at the HOCO + CH3CO+ dissociation limit. Later on, fragmentation occurs, followed by autoionisation. On the other hand, the fs-based experiment does not reveal any appreciable dynamics for the Tc isomer of PA after a 266 nm excitation because of non-favourable Franck-Condon factors at this energy. In sum, our work highlights the importance of the couplings between the parent ion vibrational modes and the dissociative channels in the vicinity of the loss ionic fragmentation thresholds.

Dual Nickel/Ruthenium Strategy for Photoinduced Decarboxylative Cross-Coupling of α,β-Unsaturated Carboxylic Acids with Cycloketone Oxime Esters.

Herein, a dual nickel/ruthenium strategy is developed for photoinduced decarboxylative cross-coupling between α,β-unsaturated carboxylic acids and cycloketone oxime esters. The reaction mechanism is distinct from previous photoinduced decarboxylation of α,β-unsaturated carboxylic acids. This reaction might proceed through a nickelacyclopropane intermediate. The C(sp2)-C(sp3) bond constructed by the aforementioned reaction provides an efficient approach to obtaining various cyanoalkyl alkenes, which are synthetically valuable organic skeletons in organic and medicinal chemistry, under mild reaction conditions. The protocol tolerates many critical functional groups and provides a route for the modification of complex organic molecules.

Sila- and Germacarboxylic Acids: Precursors for the Corresponding Silyl and Germyl Radicals.

Silicon-containing compounds are widely used as synthetic building blocks, functional materials, and bioactive reagents. In particular, silyl radicals are important intermediates for the synthesis and transformation of organosilicon compounds. Herein, we describe the first protocol for the generation of silyl radicals by photoinduced decarboxylation of silacarboxylic acids, which can be easily prepared in high yield on a gram scale and are very stable to air and moisture. Irradiation of silacarboxylic acids with blue LEDs (455 nm) in the presence of a commercially available photocatalyst releases silyl radicals, which can further react with various alkenes to give the corresponding silylated products in good-to-high yields with broad functional-group compatibility. This reaction proceeds in the presence of water, enabling efficient deuterosilylation of alkenes with D2 O as the deuterium source. Germyl radicals were similarly obtained.

Sila‐ and Germacarboxylic Acids: Precursors for the Corresponding Silyl and Germyl Radicals

AbstractSilicon‐containing compounds are widely used as synthetic building blocks, functional materials, and bioactive reagents. In particular, silyl radicals are important intermediates for the synthesis and transformation of organosilicon compounds. Herein, we describe the first protocol for the generation of silyl radicals by photoinduced decarboxylation of silacarboxylic acids, which can be easily prepared in high yield on a gram scale and are very stable to air and moisture. Irradiation of silacarboxylic acids with blue LEDs (455 nm) in the presence of a commercially available photocatalyst releases silyl radicals, which can further react with various alkenes to give the corresponding silylated products in good‐to‐high yields with broad functional‐group compatibility. This reaction proceeds in the presence of water, enabling efficient deuterosilylation of alkenes with D2O as the deuterium source. Germyl radicals were similarly obtained.

Visible- and UV-Light-Induced Decarboxylative Radical Reactions of Benzoic Acids Using Organic Photoredox Catalysts.

Photoinduced decarboxylative radical reactions of benzoic acids with electron-deficient alkenes, diborane, and acetonitrile under organic photoredox catalysis conditions and mild heating afforded adducts, arylboronate esters, and the reduction product, respectively. The reaction is thought to involve single-electron transfer promoted the generation of aryl radicals via decarboxylation. A diverse range of benzoic acids were found to be suitable substrates for this photoreaction. Only our two-molecule organic photoredox system can work well for the direct photoinduced decarboxylation of benzoic acids.

Sanger's Reagent Sensitized Photocleavage of Amide Bond for Constructing Photocages and Regulation of Biological Functions.

Photolabile groups offer promising tools to study biological processes with high spatial and temporal control. In the investigation, we designed and prepared several new glycine amide derivatives of Sanger's reagent and demonstrated that they serve as a new class of photocages for Zn2+ and an acetylcholinesterase (AChE) inhibitor. We showed that the mechanism for photocleavage of these substances involves initial light-driven cyclization between the 2,4-dinitrophenyl and glycine methylene groups to form acyl benzimidazole N-oxides, which undergo secondary photoinduced decarboxylation in association with rupture of an amide bond. The cleavage reactions proceed with modest to high quantum yields. We demonstrated that these derivatives can be used in targeted intracellular delivery of Zn2+, fluorescent imaging by light-triggered Zn2+ release, and regulation of biological processes including the enzymatic activity of carbonic anhydrase (CA), negative regulation of N-methyl-d-aspartate receptors (NMDARs), and pulse rate of cardiomyocytes. The successful proof-of-concept examples described above open a new avenue for using Sanger's reagent-based glycine amides as photocages for the exploration of complex cellular functions and signaling pathways.

New insights into the nature of short-lived paramagnetic intermediates of ketoprofen. Photo-CIDNP study

The short-lived paramagnetic particles formed during the UV irradiation of nonsteroidal anti-inflammatory drug - ketoprofen (KP) have been investigated using chemically induced dynamic nuclear polarization (CIDNP). This study answers the questions about the nature of paramagnetic particles which can be responsible for KP phototoxic effects. Phototoxic side effects of NSAIDs, according modern point of view, are associated with the action of free radicals, however, there is insufficient information regarding the nature of the radical species. In contrast, most ketoprofen photodegradation schemes include carbanion as a precursor of products. CIDNP effects analysis has shown that all the major products of KP photodegradation can form via radical pairs (RPs) involving benzyl (2′), ketyl (3′) and CO2H or CO2− free radicals and solvated electron. Radical ways of KP photodegradation include: decarboxylation via RP with benzyl radical formation (I) in non-aqueous solution and both, (I) and photoreduction with formation of ketyl radicals in the presence of water. Moreover, it was found that the photoinduced radical decarboxylation of KP represents a reversible process.