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

• residence time up to 16 times in comparison to the batch procedure, while achieving similar or higher yields. In addition, the use of inorganic bases was demonstrated to increase the reaction yield under batch conditions. Keywords: C–H functionalization; continuous-flow; organic synthesis; photoredox

• , partially due to the general interest of the community into C–H functionalization methodologies [18][19], and partially thanks to the synthetic possibilities enabled by photoredox catalysis, a field widely explored in recent years [20][21][22]. In 2018, Ngai [23][24] and Togni [25] reported simple

• photoredox protocols for the radical trifluoromethoxylation of unfunctionalized (hetero)arenes by using specifically designed CF3O radical-releasing agents (Scheme 1B). Following our long-standing interest in the development of continuous-flow approaches for C–H functionalization [18][26] and photochemical

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

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

• Stephanie G. E. Amos Marion Garreau Luca Buzzetti Jerome Waser Laboratory of Catalysis and Organic Synthesis, Ecole Polytechnique Fédérale de Lausanne, EPFL, SB ISIC LCSO, BCH 4306 1015 Lausanne, Switzerland 10.3762/bjoc.16.103 Abstract Organic dyes have emerged as a reliable class of photoredox

• -, nitrogen-, oxygen-, and sulfur-centered radicals, open-shell charged species, and sensitized organic compounds. Keywords: organic dyes; photocatalysis; photoredox catalysis; radicals; reactive intermediates; Review Introduction In the last decade, synthetic organic chemistry has experienced the

• each of these steps, the role of A or D is assumed by a redox-active agent, either the substrate, a sacrificial electron donor/acceptor, or a reactive intermediate. This approach, usually named photoredox catalysis, has known a remarkable growth in the last decade and has given access to both neutral

Accelerating fragment-based library generation by coupling high-performance photoreactors with benchtop analysis

• Quentin Lefebvre,
• Christophe Salomé and
• Thomas C. Fessard

Beilstein J. Org. Chem. 2020, 16, 982–988, doi:10.3762/bjoc.16.87

• Quentin Lefebvre Christophe Salome Thomas C. Fessard SpiroChem AG, Rosental area, WRO-1047-3, Mattenstrasse 24, 4058 Basel, Switzerland 10.3762/bjoc.16.87 Abstract Herein we report a workflow coupling photoredox-nickel dual-catalyzed N-arylation reactions to benchtop analysis for the efficient

• thus be rapidly accessed, identifying privileged or challenging scaffolds and paving the way for further exploration. Keywords: benchtop analytics; fragment-based library; heterocyclic sp2–sp3 fragments; N-arylation; photoredox-nickel dual catalysis; Introduction Heterocyclic sp2–sp3 fragments are

• initiated a high-throughput program of fragment-based library generation and after shortcomings using more classical cross-coupling conditions, we turned our attention to the photoredox-nickel dual-catalysis strategy recently reported by MacMillan and Buchwald [10]. The reported conditions use lower

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

• renewal of porphyrin applications in photocatalysis. Finally, the reaction scale in which the methodologies were developed are highlighted since this is an important parameter in the authors’ opinion. Keywords: energy transfer; photocatalysis; photooxygenation; photoredox; porphyrins; Introduction In

• photoredox and energy transfer photocatalyzed reactions. The idea of this review is also to cover representative chemical transformations and recent applications in both batch and continuous-flow conditions, and emphasizing as much as possible, the scale in which the reactions were described. It is important

• to clarify that other relevant reviews reporting applications of porphyrins in different perspectives can be found in the literature [19][20][21]. In addition, we emphasize that this review is organized into two topics. The first topic highlights the reactions that employ porphyrins as photoredox

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

• , having multiple advantages since ligand manipulation can lead to optimized photoredox properties. Unfortunately, the use of metals can pose some critical disadvantages in an organic process. Especially since the natural abundance of various noble metals that are used as photocatalysts is limited and

• supported the energy transfer pathway. Thus, the proposed triplet sensitization mechanism of the photocatalytic ATRA reaction is depicted in Scheme 25. In 2016, Ji and co-workers developed a new photoredox cross-dehydrogenative coupling (CDC) method for the α-heteroarylation of amides (α to nitrogen, e.g

Photocatalytic deaminative benzylation and alkylation of tetrahydroisoquinolines with N-alkylpyrydinium salts

• David Schönbauer,
• Carlo Sambiagio,
• Timothy Noël and
• Michael Schnürch

Beilstein J. Org. Chem. 2020, 16, 809–817, doi:10.3762/bjoc.16.74

• Dolech 2, 5612 AZ Eindhoven, The Netherlands 10.3762/bjoc.16.74 Abstract A ruthenium-catalyzed photoredox coupling of substituted N-aryltetrahydroisoquinolines (THIQs) and different bench-stable pyridinium salts was successfully developed to give fast access to 1-benzyl-THIQs. Furthermore, secondary

• (sp3) coupling; deaminative coupling; Katritzky salt; photoredox catalysis; Introduction The selective formation of new carbon–carbon bonds via direct C–H functionalization bears the potential of being a process of high efficiency [1][2][3]. Since C–H bonds are omnipresent in organic compounds it is

• ], alkynation [17][18], or allylation [19]), this method has certain drawbacks, most importantly the frequent requirement of superstoichiometric amounts of an oxidant. Hence, alternative methods were investigated and photoredox catalysis proved to be a viable option [20][21][22]. By now, several different

Photophysics and photochemistry of NIR absorbers derived from cyanines: key to new technologies based on chemistry 4.0

• Bernd Strehmel,
• Christian Schmitz,
• Ceren Kütahya,
• Yulian Pang,
• Anke Drewitz and
• Heinz Mustroph

Beilstein J. Org. Chem. 2020, 16, 415–444, doi:10.3762/bjoc.16.40

• metal ions. In this process, basically, in the presence of photoactive materials (PAs) such as photoinitiators, photosensitizers or photoredox catalysts, the photoexcitation of a photoredox system results in formation of reactive radicals. Those reactive radicals add monomer and the polymerization

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

• traditional reactivity of this compound. Here, we investigated the possibility of applying monochloroacetic acid as a substrate for photoredox catalysis with styrene to directly produce γ-phenyl-γ-butyrolactone. Instead of using nucleophilic substitution, we cleaved the carbon chlorine bond by single-electron

• form in case of fac-[Ir(ppy)3]), which was proven by mass spectrometry and EPR spectroscopy for one of the catalysts (N,N-5,10-di(2-naphthalene)-5,10-dihydrophenazine) used in this work. The generation of HCl resulting from lactone formation could be an additional problem for organometallic photoredox

• catalysts used in this reaction. In an attempt to trap one of the radical intermediates with TEMPO, we observed a compound indicating the generation of a chloromethyl radical. Keywords: ATRA; catalysis; chloroacetic acid; lactone; photoredox; Introduction Monochloroacetic acid is an industrially important

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

• compounds, including bioactive natural and nonnatural products, but also due to its impact on the discovery of pharmaceutical candidates and the total synthesis of intricate natural products. On the other hand, more recently, the field of photoredox catalysis has become an indispensable and unparalleled

• highly desirable to the scientific community. In this review, we mainly highlight the impact on, and the utility of, photoredox catalysts in inert ortho and para C–H bond functionalizations. Although a surge of research papers, including reviews, demonstrating C–H functionalizations have been published

• in this vital area of research, to our best knowledge, this is the first review that focuses on ortho and para C–H functionalizations by photoredox catalysis to provide atom- and step-economic organic transformations. We are certain that this review will act as a promoter to highlight the application

Synthesis of acremines A, B and F and studies on the bisacremines

• Nils Winter and
• Dirk Trauner

Beilstein J. Org. Chem. 2019, 15, 2271–2276, doi:10.3762/bjoc.15.219

• undergo Diels–Alder reactions with electron-rich dienophiles [13][14][15][16][17], treatment of 5 with Fukuzumi’s catalyst [18] under illumination with blue light only led to decomposition of the starting material (Table 1, entry 15). Notably, a photoredox catalyst with a lower oxidation potential could

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

• co-workers [117] explored a simple and facile method to access δ-trifluoromethylated carboxamides and sulfonamides through a copper-catalyzed 1,5-hydrogen atom transfer (Scheme 58). Other catalysts: In 2013, Gouverneur and co-workers [118] described a photoredox-based catalytic approach to afford

• oxidative decarboxylation. Then, Cu(CF3)2 provides a CF3 group to alkyl radicals to obtain the final product. Very recently, MacMillan et al. [120] discovered an efficient approach to the decarboxylative trifluoromethylation of aliphatic carboxylic acids via the combination of photoredox and copper

• 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

Friedel–Crafts approach to the one-pot synthesis of methoxy-substituted thioxanthylium salts

• Kenta Tanaka,
• Yuta Tanaka,
• Mami Kishimoto,
• Yujiro Hoshino and
• Kiyoshi Honda

Beilstein J. Org. Chem. 2019, 15, 2105–2112, doi:10.3762/bjoc.15.208

• . Keywords: Friedel–Crafts reaction; metal-free conditions; one-pot synthesis; photoredox catalyst; thioxanthylium salt; Introduction Thioxanthylium salts are one of the important structural motifs found in biologically active compounds and photochemical materials [1][2][3][4][5][6][7][8]. Owing to these

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

• light photoredox catalysts and characterized by methods of optical spectroscopy and electrochemistry in comparison with one unsubstituted naphthalene diimide as reference. The core-substituted naphthalene diimides differ by the alkyl groups at the imide nitrogens and at the nitrogens of the two

• substituents at the core in order to enhance their solubility in DMF and thereby enhance their photoredox catalytic potential. The 1-ethylpropyl group as rather short and branched alkyl substituent at the imide nitrogen and the n-propyl group as short and unbranched one at the core amines yielded the best

• potential was estimated to be approximately +1.0 V (vs SCE) which is sufficient to photocatalyze typical organic reactions. The photoredox catalytic activity in the visible light range was tested by the α-alkylation of 1-octanal as benchmark reaction. Irradiations were performed with LEDs in the visible

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

• trimethylsilyl trifluoromethanesulfonate (TMSOTf) in a diastereoselective and stepwise manner. This novel methodology provides a shorter access to the intermediate 97, which is a key intermediate for the synthesis of triptolide. Recently, photoredox catalysis has emerged as a powerful and high-yielding method

• 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

• under the optimal photoredox conditions to provide tetracyclic intermediate 19i (dr = 1:1, Scheme 8, route L), with a cis A-/B-ring connection rather than the desired trans connection. Treatment of 19i with H2SO4, followed by RuCl2(PPh3)3-catalyzed double bond isomerization gave the known intermediate

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

• describe a method for alkene oxyamination and diamination that utilizes simple carbamate and urea groups as nucleophilic heteroatom donors. This method uses a tandem copper–photoredox catalyst system that is operationally convenient. The identity of the terminal oxidant is critical in these studies. Ag(I

• ) salts proved to be unique in their ability to turn over the copper cocatalyst without deleteriously impacting the reactivity of the organoradical intermediates. Keywords: copper; diamination; oxidative functionalization; oxyamination; photoredox catalysis; radical; Introduction Over the past decade, a

• photoinduced electron transfer processes. A major theme of research that has emerged from these studies is the application of various cocatalysts to intercept the organoradical intermediates of photoredox reactions and modulate their subsequent reactivity [5][6]. The combination of photoredox catalysis with

Oxidative radical ring-opening/cyclization of cyclopropane derivatives

• Yu Liu,
• Qiao-Lin Wang,
• Zan Chen,
• Cong-Shan Zhou,
• Bi-Quan Xiong,
• Pan-Liang Zhang,
• Chang-An Yang and
• Quan Zhou

Beilstein J. Org. Chem. 2019, 15, 256–278, doi:10.3762/bjoc.15.23

• photoredox catalysis oxidative radical ring-opening and cyclization of cyclopropyl olefins 83 with bromides 84 for the synthesis of partially saturated naphthalenes 85 in moderate to excellent yields (Scheme 19) [97]. It was the first example for alkylation, ring-opening and cyclization cascade reaction of

• the cyclopropyl olefins under photoredox catalysis. The alkylation reagents could be extended to other bromides, such as monofluoro-substituted bromides, trifluoro-substituted bromides, bromoacetonitrile and bromomalonate. This alkylation/ring-opening/cyclization was carried out by using Ir(ppy)2

• (dtbbpy)PF4 as photocatalyst, and K2HPO4 as base in MeCN under the irradiation of 24 W blue LED light at room temperature for 12–36 h. A plausible mechanism is shown in Scheme 19. Firstly, the substrate 84a underwent oxidative quenching under the action of an iridium photoredox catalyst to afford the

N-Arylphenothiazines as strong donors for photoredox catalysis – pushing the frontiers of nucleophilic addition of alcohols to alkenes

• Fabienne Speck,
• David Rombach and
• Hans-Achim Wagenknecht

Beilstein J. Org. Chem. 2019, 15, 52–59, doi:10.3762/bjoc.15.5

• Fabienne Speck David Rombach Hans-Achim Wagenknecht Institute of Organic Chemistry, Karlsruhe Institute of Technology (KIT), Fritz-Haber-Weg 6, 76131 Karlsruhe, Germany 10.3762/bjoc.15.5 Abstract A new range of N-phenylphenothiazine derivatives was synthesized as potential photoredox catalysts to

• broaden the substrate scope for the nucleophilic addition of methanol to styrenes through photoredox catalysis. These N-phenylphenothiazines differ by their electron-donating and electron-withdrawing substituents at the phenyl group, covering both, σ and π-type groups, in order to modulate their

• absorbance and electrochemical characteristics. Among the synthesized compounds, alkylaminylated N-phenylphenothiazines were identified to be highly suitable for photoredox catalysis. The dialkylamino substituents of these N-phenylphenothiazines shift the estimated excited state reduction potential up to

Organometallic vs organic photoredox catalysts for photocuring reactions in the visible region

• Aude-Héloise Bonardi,
• Frédéric Dumur,
• Guillaume Noirbent,
• Jacques Lalevée and
• Didier Gigmes

Beilstein J. Org. Chem. 2018, 14, 3025–3046, doi:10.3762/bjoc.14.282

• from adhesives, coatings, packaging materials, inks, paints, optics, 3D printing, microelectronics or textiles. From a synthetic viewpoint, photoredox catalysis, originally developed for organic chemistry, has recently been applied to the polymer synthesis, constituting a major breakthrough in polymer

• chemistry. Thanks to the development of photoredox catalysts of polymerization, a drastic reduction of the amount of photoinitiators could be achieved, addressing the toxicity and the extractability issues; high performance initiating abilities are still obtained due to the catalytic approach which

• regenerates the catalyst. As it is a fast-growing field, this review will be mainly focused on an overview of the recent advances concerning the development of organic and organometallic photoredox catalysts for the photoreticulation of multifunctional monomers for a rapid and efficient access to 3D polymer

Photocatalyic Appel reaction enabled by copper-based complexes in continuous flow

• Clémentine Minozzi,
• Jean-Christophe Grenier-Petel,
• Shawn Parisien-Collette and
• Shawn K. Collins

Beilstein J. Org. Chem. 2018, 14, 2730–2736, doi:10.3762/bjoc.14.251

• photocatalyst, Cu(tmp)(BINAP)BF4, was found to be active in a photoredox Appel-type conversion of alcohols to bromides. The catalyst was identified from a screening of 50 complexes and promoted the transformation of primary and secondary alcohols to their corresponding bromides and carboxylic acids to their

• providing 2 (54–87% yield, not including dppf-based complexes). Interestingly, the best catalyst for the transformation (Cu(tmp)(BINAP)BF4, 99% of 2) was a poor catalyst for a previously reported photoredox reaction [27]. It should be noted that Cu(tmp)(BINAP)+ possesses an excited state reduction potential

Synthesis of aryl sulfides via radical–radical cross coupling of electron-rich arenes using visible light photoredox catalysis

• Amrita Das,
• Mitasree Maity,
• Simon Malcherek,
• Burkhard König and
• Julia Rehbein

Beilstein J. Org. Chem. 2018, 14, 2520–2528, doi:10.3762/bjoc.14.228

• showed that an aryl disulfide could be cleaved by irradiation with visible light [49]. Some spectroscopic investigations (Figure 3) gave valuable information about the mechanism of the photoredox catalytic cycle. The luminescence intensity of [Ir(dF(CF3)ppy)2(dtbpy)]PF6 was quenched upon successive

Cobalt- and rhodium-catalyzed carboxylation using carbon dioxide as the C1 source

• Tetsuaki Fujihara and
• Yasushi Tsuji

Beilstein J. Org. Chem. 2018, 14, 2435–2460, doi:10.3762/bjoc.14.221

• presence of [Ir(ppy)(dtbpy)](PF6) and iPr2NEt as photoredox catalyst and a sacrificial reagent, respectively, in acetonitrile under an atmospheric pressure of CO2 (Scheme 20). 1-Phenyl-1-propyne (16n) afforded hydrocarboxylated products as a mixture of regio- and stereoisomers. 4-Octyne (16b) afforded the

• reaction mechanism for these reactions. First, the Co(II) precursor is reduced to Co(I) A by the aid of an Ir photoredox catalyst and an amine under irradiation. The oxidative cyclization of A with 23 and CO2 affords cobaltacycle B (step a). Next, the protonation of B affords an intermediate C (step b

• et al. reported the Rh-catalyzed hydrocarboxylation of alkenes driven by visible-light irradiation conditions in the presence of a photoredox catalyst (Scheme 37) [75]. A model reaction using 4-cyanostyrene (40a) was carried out using iPrNEt2 as a sacrificial electron donor in the presence of [Ru(bpy

Microfluidic light-driven synthesis of tetracyclic molecular architectures

• Javier Mateos,
• Nicholas Meneghini,
• Marcella Bonchio,
• Nadia Marino,
• Tommaso Carofiglio,
• Xavier Companyó and
• Luca Dell’Amico

Beilstein J. Org. Chem. 2018, 14, 2418–2424, doi:10.3762/bjoc.14.219

• molecules. Keywords: [4 + 2] photoenol; cycloaddition; flow chemistry; microfluidic photoreactor; photoredox catalysis; synthetic photochemistry; Introduction In recent years synthetic photochemistry has become highly sophisticated [1]. The opportunity of using renewable energy sources to transform and

Bioinspired cobalt cubanes with tunable redox potentials for photocatalytic water oxidation and CO₂ reduction

• Zhishan Luo,
• Yidong Hou,
• Jinshui Zhang,
• Sibo Wang and
• Xinchen Wang

Beilstein J. Org. Chem. 2018, 14, 2331–2339, doi:10.3762/bjoc.14.208

• photocatalytic conversions has been the Achilles’ heel of solar energy utilization. Here, we report on a chemical approach based on ligand designed architectures to fabricate unique structural molecular catalysts coupled with appropriate light harvesters (e.g., carbon nitride and Ru(bpy)32+) for photoredox

• characteristics for a molecular catalyst by selective ligand modification. This work demonstrates a modulation method for fabricating effective, stable and earth-abundant molecular catalysts, which might facilitate further innovation in the function-led design and synthesis of cubane clusters for photoredox

• highly active for both water oxidation and CO2 reduction reactions, which is in good agreement with the results of the optical, CV and LSV measurements. Importantly, the photoredox functions of the molecular complexes can be modulated deliberately by ligand substitutions with different electronic

One-pot synthesis of epoxides from benzyl alcohols and aldehydes

• Edwin Alfonzo,
• Jesse W. L. Mendoza and
• Aaron B. Beeler

Beilstein J. Org. Chem. 2018, 14, 2308–2312, doi:10.3762/bjoc.14.205

• into carbonyls [8][9][10][11][12][13][14][15][16][17], and application to cascade or domino reactions [18][19]. More recently, our group has used benzyl epoxides for the photoredox generation of carbonyl ylides which are leveraged in the synthesis of cyclic ethers [20]. This work has led us to search