Metal-free synthesis of biarenes via photoextrusion in di(tri)aryl phosphates

• Hisham Qrareya,
• Lorenzo Meazza,
• Stefano Protti and
• Maurizio Fagnoni

Beilstein J. Org. Chem. 2020, 16, 3008–3014, doi:10.3762/bjoc.16.250

• the presence of increasing amounts of TFE (up to 20% v/v, continuous line). Synthesis of biarenes via a) photogenerated triplet aryl cations and aryl radicals (PC = photocatalyst), b) intramolecular free radical ipso substitution, c) thermally catalyzed extrusion of CO and SO2, d) photoinduced

Dawn of a new era in industrial photochemistry: the scale-up of micro- and mesostructured photoreactors

• Emine Kayahan,
• Mathias Jacobs,
• Leen Braeken,
• Leen C.J. Thomassen,
• Simon Kuhn,
• Tom van Gerven and
• M. Enis Leblebici

Beilstein J. Org. Chem. 2020, 16, 2484–2504, doi:10.3762/bjoc.16.202

• packed bed reactor so that several microchannels were created among the beads. Glass beads were coated with a TiO2 photocatalyst. The photoreactor was illuminated with 192 LEDs that could provide 100 mW of power each. The distance between the LED board and the reactor was adjusted to give a uniform

• constant. Many photoreactions are heterogeneous, which means that the reaction requires the presence of at least two phases. Heterogeneous reactions require either a solid photocatalyst in a liquid medium or gas and liquid phases as the reactants. The mass transport and mixing gain extra importance in such

• systems. The mass transport is usually represented by the ratio of catalyst surface area to the reaction volume in photocatalytic systems. The photocatalyst could either be mixed with the reactants and fed into the reactor (slurry systems) or immobilized on a reactor surface. Slurry reactors remain the

Recent developments in enantioselective photocatalysis

• Callum Prentice,
• James Morrisson,
• Andrew D. Smith and
• Eli Zysman-Colman

Beilstein J. Org. Chem. 2020, 16, 2363–2441, doi:10.3762/bjoc.16.197

• 1 with amine catalyst 3 to give enamine intermediate 4. The initiation step is proposed to be a reductive quench of the photocatalyst using 4 as a sacrificial reductant to give [Ru]•−, which can then reduce 2 to give electrophilic radical 2•. Addition of 2• to another molecule of 4 generates α-amino

• ], electron-deficient arenes [24], and nitriles [25]. Additionally, Cozzi recently applied a novel aluminium-based photocatalyst 9 to this reaction, as an earth-abundant metal alternative albeit with slightly reduced enantioselectivities (8 examples, up to 96:4 er) [26]. Interestingly, as with some other

• reductively quenches the photocatalyst to form enaminyl radical 13•+. However, in this reaction 13•+ can then add to the alkene to give an alkyl radical 14•+, followed by hydrogen atom abstraction from the thiol, acting as a HAT catalyst, to give iminium ion intermediate 15. Hydrolysis of 15 generates the

Photosensitized direct C–H fluorination and trifluoromethylation in organic synthesis

• Shahboz Yakubov and
• Joshua P. Barham

Beilstein J. Org. Chem. 2020, 16, 2151–2192, doi:10.3762/bjoc.16.183

• reactions proceed under photoredox catalysis (PRC), involving Dexter electron transfer. Such photoredox reactions begin with the excitation of the photocatalyst (PC) by visible light, followed by a single-electron transfer (SET) between the excited photocatalyst and another molecule (quencher, Scheme 2A

• ). An unfortunate consequence of this is that there are many organic molecules with redox potentials that lie beyond the range of those of the excited photocatalyst [87]. The transiently generated (ultralow concentration of) the excited-state catalyst does not persist long enough even for slightly

• which the excited state photocatalyst participates directly in HAT with the substrate (Scheme 2B), herein termed PHAT [88]. iii) Photochemical reactions where the photosensitization catalyst (PSCat) engages in Dexter energy transfer (typically TTET) with the substrate (or fluorinating reagent) to induce

When metal-catalyzed C–H functionalization meets visible-light photocatalysis

• Lucas Guillemard and
• Joanna Wencel-Delord

Beilstein J. Org. Chem. 2020, 16, 1754–1804, doi:10.3762/bjoc.16.147

• , few examples have been reported in which the photoredox process modifies the oxidation state of a catalyst [55][56]. Subsequently, C–H activation protocols benefiting from mild photocatalytic reoxidation have spread rapidly [60][61][62]. In such a case, a photocatalyst (PC) is introduced in the

• that both, the excited Ir photocatalyst and the superoxide anion generated during the transformation, were able to oxidize the low-valent Pd(0) species resulting from the reductive elimination (Figure 6). Under such dual catalysis protocol, various oxidant-sensitive functional groups were tolerated

• -functionalization viewpoint, thus furnishing a large panel of compounds in excellent to good yields. This C–H olefination of arenes was performed under aerobic conditions in order to reoxidize the photocatalyst (Figure 8). Interestingly, the desired products were also delivered while using a stoichiometric amount

Photoredox-catalyzed silyldifluoromethylation of silyl enol ethers

• Vyacheslav I. Supranovich,
• Vitalij V. Levin and
• Alexander D. Dilman

Beilstein J. Org. Chem. 2020, 16, 1550–1553, doi:10.3762/bjoc.16.126

• )trimethylsilane followed by a reduction of the primary products with sodium borohydride is described. An 18 W, 375 nm LED was used as the light source. The reaction is performed in the presence of a gold photocatalyst, which effects the generation of a (trimethylsilyl)difluoromethyl radical via cleavage of the

• source of hydrogen [21]. We thought that silane 1 could couple with silyl enol ethers in the presence of a photocatalyst affording fluoroalkylation products. Indeed, silyl enol ethers were found to be good acceptors of fluorinated radicals, and the resultant silyloxy-substituted radicals underwent single

• strongly reducing catalysts may be associated with the ability of gold to interact with the bromine atom of silane 1 followed by inner-sphere electron transfer [27]. The radical then attacks silyl enol ether 2, and the subsequent silyloxy-substituted radical is oxidized by the photocatalyst to generate the

Heterogeneous photocatalysis in flow chemical reactors

• Christopher G. Thomson,
• Ai-Lan Lee and
• Filipe Vilela

Beilstein J. Org. Chem. 2020, 16, 1495–1549, doi:10.3762/bjoc.16.125

• the molar attenuation coefficient of the photocatalyst (ε), its concentration (c), and the optical path length (l). This also applies to immobilising an HPCat in a flow reactor, which generally confines and concentrates the material within a transparent vessel with high surface-to-volume ratio

• solution, completing the photocatalyst cycle. Charge carriers must overcome competing processes that result in the immobilisation and recombination of charge carriers. The photogenerated electron/hole pair will spontaneously undergo bulk or surface recombination if they cannot efficiently separate, which

• dependent on the temperature and electronic disorder as each hop requires the reorganisation of the molecules in the chain [115]. A particularly popular organic semiconductor photocatalyst in the recent literature is graphitic carbon nitride (g-C3N4) [23]. g-C3N4 was one of the first synthetic polymers

Photocatalyzed syntheses of phenanthrenes and their aza-analogues. A review

• Alessandra Del Tito,
• Havall Othman Abdulla,
• Davide Ravelli,
• Stefano Protti and
• Maurizio Fagnoni

Beilstein J. Org. Chem. 2020, 16, 1476–1488, doi:10.3762/bjoc.16.123

• photocatalyst, have revolutionized the way chemists can arrive to important chemical scaffolds [24][25][26]. Indeed, the photocatalytic approach combines unparalleled mild conditions, due to the use of photons as traceless reagents that leave no residue behind [27][28], with the exploitation of rather

• heteroarene analogues via the intermediacy of a radical. However, some interesting approaches carried out under photomediated or photocatalyst-free conditions have been likewise included for the sake of completeness. Review 1 Synthesis of phenanthrenes The photocatalyzed synthesis of the phenanthrene skeleton

• -bromochalcones (Scheme 3). Thus, compounds 3.1a–d underwent a one-electron reduction by the excited photocatalyst fac-Ir(ppy)3. Upon bromide anion loss, the α-keto vinyl radicals 3.2·a–d were then formed, which smoothly added onto the vicinal aromatic ring in an intramolecular fashion, affording phenanthrene

An overview on disulfide-catalyzed and -cocatalyzed photoreactions

• Yeersen Patehebieke

Beilstein J. Org. Chem. 2020, 16, 1418–1435, doi:10.3762/bjoc.16.118

• catalytic abilities: they can be a photocatalyst, HAT catalyst, initiator, or cocatalyst in organic synthesis. The thiyl radicals (RS•) formed under illumination conditions have the unique ability of promote radical bond-forming reactions. Their ability to reversibly add to unsaturated bonds, promoting a

• . Huang and co-workers proposed a polar radical crossover cycloaddition mechanism for this Diels–Alder cycloaddition (Scheme 6). The electron transfer from the electron-rich styrene 14 to the activated acridinium photocatalyst 15 oxidizes the styrene 14 to form the styrene radical 16 and the acridine

• radical 17 (Mes–Acr–Ph•). The subsequent reaction of the formed styrene radical 16 with another styrene 18 gives the radical species 19 and the reoxidation of the acridine radical 17 by a thiyl radical, which is generated by the homolysis of diphenyl disulfide, regenerating the photocatalyst. In a

Distinctive reactivity of N-benzylidene-[1,1'-biphenyl]-2-amines under photoredox conditions

• Shrikant D. Tambe,
• Kwan Hong Min,
• Naeem Iqbal and
• Eun Jin Cho

Beilstein J. Org. Chem. 2020, 16, 1335–1342, doi:10.3762/bjoc.16.114

• -coupled single-electron transfer in the presence of an Ir photocatalyst. On the other hand, symmetrical 1,2-diamines were selectively produced from the same starting materials by the judicious choice of the reaction conditions, showcasing the distinct reactivity of N-benzylidene-[1,1'-biphenyl]-2-amines

• amount of Cy2NMe was critical for achieving selectivity, and less than two equivalents of Cy2NMe gave greater amounts of the homocoupled product 3a (Table 1, entry 10). Control experiments showed that the photocatalyst, amine base, and light source are integral aspects of the reaction (Table 1, entries

• produced the reduced amine product 4a in 67% yield (Scheme 4) [17][18][58][59][60][61]. Based on these observations, a plausible reaction mechanism was proposed for the developed transformation (Scheme 5). Upon visible-light irradiation, the excited photocatalyst [IrIII]* is formed and is reductively

Photocatalytic trifluoromethoxylation of arenes and heteroarenes in continuous-flow

• Alexander V. Nyuchev,
• Ting Wan,
• Borja Cendón,
• Carlo Sambiagio,
• Job J. C. Struijs,
• Michelle Ho,
• Moisés Gulías,
• Ying Wang and
• Timothy Noël

Beilstein J. Org. Chem. 2020, 16, 1305–1312, doi:10.3762/bjoc.16.111

• Ir photocatalyst was tested under blue light irradiation, but a poor 10% yield was obtained. Experiments in the absence of photocatalyst under violet or blue light gave respectively 17% and 0% yield. The little product obtained with 400 nm light can be explained by the photodecomposition of 1, which

Oxime radicals: generation, properties and application in organic synthesis

• Igor B. Krylov,
• Stanislav A. Paveliev,
• Alexander S. Budnikov and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2020, 16, 1234–1276, doi:10.3762/bjoc.16.107

• aromatic (products 88a–d) and aliphatic (products 88e,f) substituents are applicable. Oximes with an isoindoline or tetrahydroisoquinoline fragment also undergo this transformation to give substituted oxadiazolines (products 88g,h). The authors note that T(p-F)PPT plays the role of a photocatalyst that

Photocatalysis with organic dyes: facile access to reactive intermediates for synthesis

• Stephanie G. E. Amos,
• Marion Garreau,
• Luca Buzzetti and
• Jerome Waser

Beilstein J. Org. Chem. 2020, 16, 1163–1187, doi:10.3762/bjoc.16.103

• photocatalysts interact with organic molecules via three main pathways: electron transfer (ET), EnT, and atom transfer (AT). In the first case (Scheme 1, box 1), the excited photocatalyst (PC*) undergoes a single-electron transfer (SET) with a suitable electron acceptor A or electron donor D. In an oxidative

• quenching cycle, PC* acts as a reductant donating an electron to A. This generates the oxidized form of the photocatalyst, PC•+, and a reduced acceptor, A•−. Alternatively, in a reductive quenching cycle, PC* acts as an oxidant promoting an SET oxidation of the electron donor D. This leads to the reduced

• photocatalyst PC•− and the oxidized donor D•+. Following this initial SET, a second electron transfer must occur to ensure the catalyst turnover and restore the ground state photocatalyst: PC•+ needs to be reduced by an electron donor D, whereas PC•− needs to undergo an oxidation by an electron acceptor A. In

Recent applications of porphyrins as photocatalysts in organic synthesis: batch and continuous flow approaches

• Rodrigo Costa e Silva,
• Luely Oliveira da Silva,
• Aloisio de Andrade Bartolomeu,
• Timothy John Brocksom and
• Kleber Thiago de Oliveira

Beilstein J. Org. Chem. 2020, 16, 917–955, doi:10.3762/bjoc.16.83

• ) [1][2][3]. This effect limits the penetration of photons to only a short distance into the reaction vessel, provoking increases of the reaction time, photocatalyst loading, byproducts, overheating and so on. Notably, the use of continuous-flow reactors for photochemical applications allows us to

• overcome these issues, and leads to a drastic reduction of reaction time, lower photocatalyst loadings, minimization of the formation of byproducts [2] and uses visible light, which is considered a clean reagent [4]. Overall, visible light combined with organic photocatalysts such as porphyrinoids, make

• standard reduction potentials for the photocatalyst in both ground and excited states [14]. For example, the oxidation potentials for ground [E1/2(TPP+•/TPP)] and excited states [E1/2(TPP+•/TPP*)] of tetraphenylporphyrin (TPP), whose electrochemical data are available [10], are +1.03 V and −0.42 V

A method to determine the correct photocatalyst concentration for photooxidation reactions conducted in continuous flow reactors

• Clemens R. Horn and
• Sylvain Gremetz

Beilstein J. Org. Chem. 2020, 16, 871–879, doi:10.3762/bjoc.16.78

• Clemens R. Horn Sylvain Gremetz Corning European Technology Center, 7 Bis Avenue de Valvins, F-77215 Avon Cedex, France 10.3762/bjoc.16.78 Abstract When conducting a photooxidation reaction, the key question is what is the best amount of photocatalyst to be used in the reaction? This work

• demonstrates a fast and simple method to calculate a reliable concentration of the photocatalyst that will ensure an efficient reaction. The determination is based on shifting the calculation away from the concentration of the compound to be oxidized to utilizing the limitations on the total light dose that

• facilitate that other factors become more important. Notably, an exact description of the photoflow setup is now crucial to ensure reproducible experiments [20][21]. Results and Discussion The effect of 1 mol % photocatalyst This work was accomplished using the Corning® Advanced-Flowtm Lab Photo Reactor

Aldehydes as powerful initiators for photochemical transformations

• Maria A. Theodoropoulou,
• Nikolaos F. Nikitas and
• Christoforos G. Kokotos

Beilstein J. Org. Chem. 2020, 16, 833–857, doi:10.3762/bjoc.16.76

• presented. Keywords: aldehyde; green chemistry; photochemistry; photoinitiation; sustainable chemistry; Introduction Photochemistry, and especially photoredox catalysis have altered the way that modern researchers treat radical species [1][2][3][4]. In most cases, a metal-based photocatalyst is employed

• -bromobenzaldehyde (96) were also effective as photocatalysts, providing, however, a lower product yield. On the contrary to aromatic aldehydes, benzophenone, which was also tested as a photocatalyst, could promote the reaction only when used in superstoichiometric amounts. This way, 4-anisaldehyde (52) was found to

• UV as the light source and a nickel catalyst [60]. The authors suggested that the product 172, a substituted benzophenone, could act as the photocatalyst and the hydrogen atom transfer agent in this reaction (Scheme 40). They optimized the reaction conditions with regard to the nickel catalyst, the

Recent advances in photocatalyzed reactions using well-defined copper(I) complexes

• Mingbing Zhong,
• Xavier Pannecoucke,
• Philippe Jubault and
• Thomas Poisson

Beilstein J. Org. Chem. 2020, 16, 451–481, doi:10.3762/bjoc.16.42

• ) photocatalyst (Scheme 1) [16]. The [Cu(I)(dap)2]Cl complex had a strong absorption under irradiation at 530 nm using a green LED. Different organic halides and alkenes were reacted, leading to the product by an ATRA reaction pathway with moderate to good yield at room temperature (Scheme 1). The authors

• copper photocatalyst initiated the formation of the azidyl radical, which abstracted the benzylic hydrogen atom from the substrate. Then, the benzylic radical reacted with the Zhdankin reagent, producing the azidated product and propagating the radical chain through the reaction of the iodane radical

• radical was oxidized to the corresponding carbocation, regenerating the photocatalyst in the ground state. The benzylic carbocation was finally trapped with MeOH, which was used as the solvent to form the trifluoromethyl methoxylated product. In the same publication, Dilman and co-workers reported the

Visible-light-induced addition of carboxymethanide to styrene from monochloroacetic acid

• Kaj M. van Vliet,
• Nicole S. van Leeuwen,
• Albert M. Brouwer and
• Bas de Bruin

Beilstein J. Org. Chem. 2020, 16, 398–408, doi:10.3762/bjoc.16.38

• rapid redox reaction between the oxidant and the reducing agent instead of converting the substrate). Excitation of the photocatalyst, on the other hand, allows continuous formation of low concentrations of both oxidized and reduced radical forms of the substrate(s), and the excited catalysts (and/or

• photosensitizer. Because the use of polar solvents did not lead to the desired reactivity, we turned to nonpolar solvents. Since [Cu(dap)2]Cl is insoluble in nonpolar solvents, we continued with the more reducing fac-[Ir(ppy)3] photocatalyst. The choice of benzene as a solvent led to a significant formation of

• organic photocatalyst, showing hyperfine interactions with two equivalent nitrogen nuclei (giso = 2.0032; ANiso = 18.6 MHz). The HRMS of this species showed the mass of the catalyst, thus confirming that the oxidized catalyst precipitates as a salt from solution when using benzene as a solvent. Based on

Recent developments in photoredox-catalyzed remote ortho and para C–H bond functionalizations

• Rafia Siddiqui and
• Rashid Ali

Beilstein J. Org. Chem. 2020, 16, 248–280, doi:10.3762/bjoc.16.26

• ]. In photoredox catalysis, visible light gets absorbed by the photocatalyst (PC), which transitions into a photoexcited state (*PC) that can undergo either energy transfer or redox pathways. As can be seen in Figure 4, the redox pathway consists of reductive and oxidative quenching pathways

• reaction conditions. Similar to Scheme 2, there was no product obtained without a semiconductor photocatalyst. Therein, they utilized the efficient photoredox catalysts 16 (band gap: 2.4 eV) and 17 (band gap: 2.6–3.0 eV). However, better results were obtained with a heterogeneous semiconductor, photoredox

• seen in Figure 8, the mechanism of the reaction commences with the deprotonation of the biphenyl carboxylic acid 36, followed by the reaction of 38 with dimethyl dicarbonate (DMDC) to generate compound 39. On the other hand, the photocatalyst is excited by metal–ligand charge transfer, which produces

Recent advances in transition-metal-catalyzed incorporation of fluorine-containing groups

• Xiaowei Li,
• Xiaolin Shi,
• Xiangqian Li and
• Dayong Shi

Beilstein J. Org. Chem. 2019, 15, 2213–2270, doi:10.3762/bjoc.15.218

• catalysis (Scheme 61). The method tolerates a myriad of primary, secondary and tertiary carboxylic acids and provides the corresponding CF3 analogue in good to excellent yields. Details of the proposed dual copper–photoredox cycle are shown in Scheme 61. The Ir(III) photocatalyst Ir[dF(CF3)ppy]2(4,4

• Cu(II) complex 6, along with reduced Ir(II) photocatalyst 7. The resulting carboxyl radical extrudes CO2 and sequentially recombines to generate Cu(III) species 9. At this stage, SET from 7 to 9 closes the photoredox catalytic cycle and produces an alkylcopper(II) species 10. Under the addition of

• efficient method to access ortho-CF3 acetanilides and anilines (Scheme 66b). Recently, Wang and co-workers [127] reported a visible-light-induced Pd-catalyzed ortho-trifluoromethylation of acetanilides. Without the need of an external photocatalyst and additive, various N-substituted anilides and

Naphthalene diimides with improved solubility for visible light photoredox catalysis

• Barbara Reiß and
• Hans-Achim Wagenknecht

Beilstein J. Org. Chem. 2019, 15, 2043–2051, doi:10.3762/bjoc.15.201

• species – a photocatalyst. If the interacting mode between the sensitizer and the reactant is via charge transfer, it is named photoredox catalysis. This research field has been established over the past decade [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20]. In principle, it is a

A review of the total syntheses of triptolide

• Xiang Zhang,
• Zaozao Xiao and
• Hongtao Xu

Beilstein J. Org. Chem. 2019, 15, 1984–1995, doi:10.3762/bjoc.15.194

• cationic polyene cyclization, transition-metal- or photocatalyst-mediated radical polyene cyclization [72]. The key to such transformation is to install a proper initiator within the substrate such as an allylic alcohol, an acetal, an aziridine, an N-acetal, a hydroxylactam, or a 1,3-dicarbonyl moiety. van

• oxidation of the tertiary radical and reduction of the [Au-Au]3+ ion could give the cyclization product and regenerate the dimeric gold photocatalyst. Later, the utility of this photoredox methodology was demonstrated in a concise formal synthesis of triptolide (1) via the reaction of bromobutenolide 19

Multicomponent reactions (MCRs): a useful access to the synthesis of benzo-fused γ-lactams

• Edorta Martínez de Marigorta,
• Jesús M. de Los Santos,
• Ana M. Ochoa de Retana,
• Javier Vicario and
• Francisco Palacios

Beilstein J. Org. Chem. 2019, 15, 1065–1085, doi:10.3762/bjoc.15.104

• , including a thiophene derivative. With the aid of several dedicated experiments, the researchers proposed a mechanism initiated by the formation of an arylsulfonyl radical 72, which then would add to the alkene moiety in 67 to produce a radical intermediate 73 (Scheme 22). The photocatalyst-assisted

Dirhodium(II)-catalyzed [3 + 2] cycloaddition of N-arylaminocyclopropane with alkyne derivatives

• Wentong Liu,
• Yi Kuang,
• Zhifan Wang,
• Jin Zhu and
• Yuanhua Wang

Beilstein J. Org. Chem. 2019, 15, 542–550, doi:10.3762/bjoc.15.48

• cycloaddition chemistry based on compound 1. Zheng et al. [7] first reported on the [3 + 2] cycloaddition reaction of 1 with an alkene or alkyne mediated by visible light by the aid of the photocatalyst [Ru(bpz)3](PF6)2. Our group reported the metal catalyst itself, particularly the dinuclear rhodium complex

Tandem copper and photoredox catalysis in photocatalytic alkene difunctionalization reactions

• Nicholas L. Reed,
• Madeline I. Herman,
• Vladimir P. Miltchev and
• Tehshik P. Yoon

Beilstein J. Org. Chem. 2019, 15, 351–356, doi:10.3762/bjoc.15.30

• photocatalyst can be coupled to the reduction of Cu(I) to Cu(0), which can be observed precipitating from solution over the course of the reaction. Copper(II) salts have been demonstrated to be convenient terminal oxidants in a variety of synthetically useful catalytic reactions [23][24][25][26]. They are

• of carbamate 1 (Table 1), a reaction we had previously studied under stoichiometric Cu(II) conditions and found to proceed in good yield using 2.5 mol % 2,4,6-triphenylpyrylium tetrafluoroborate (TPPT, 3) as a photocatalyst and 1.2 equiv of Cu(TFA)2 as a stoichiometric oxidant. We lowered the loading

• nitrogen atom source (16–18). Finally, alkene diamination is also readily achieved using N-phenylureas as nucleophiles, although acridinium photocatalyst 6 afforded modestly higher yields in these reactions (19–21). A complete mechanistic picture of this reaction will require additional experimentation