Transition-metal-catalyzed C–H bond activation as a sustainable strategy for the synthesis of fluorinated molecules: an overview

• Louis Monsigny,
• Floriane Doche and
• Tatiana Besset

Beilstein J. Org. Chem. 2023, 19, 448–473, doi:10.3762/bjoc.19.35

• approaches, the transition-metal-catalyzed functionalization of various scaffolds with a panel of fluorinated groups (XRF, X = S, Se, O) offered straightforward access to high value-added compounds. This review will highlight the main advances made in the field with the transition-metal-catalyzed

• [6][7][8][9][10][11]. Among them [2][5][12][13][14][15][16][17][18], the direct functionalization of a simple C–H bond by transition-metal catalysis [19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35][36][37][38][39][40][41][42][43] became an important tool offering new

• retrosynthetic disconnections. In this context, a strong interest from the scientific community was shown towards the challenging synthesis of fluorinated molecules by transition-metal-catalyzed C–H bond activation [44][45][46][47][48][49][50], allowing the functionalization of complex molecules and even for

Mechanochemical solid state synthesis of copper(I)/NHC complexes with K₃PO₄

• Ina Remy-Speckmann,
• Birte M. Zimmermann,
• Mahadeb Gorai,
• Martin Lerch and
• Johannes F. Teichert

Beilstein J. Org. Chem. 2023, 19, 440–447, doi:10.3762/bjoc.19.34

• generally there are many different synthetic routes to transition metal/NHC complexes [7][8][9][10][11][12][13][14][15] not all of them are applicable to the preparation of copper(I)/NHC compounds (Scheme 1) [5][6][13][16][17][18][19]. Generally, the so-called direct routes via the appropriate imidazol(in

• ) (Scheme 1d). In some cases, this transmetallation step is carried out in situ [14][15][29][30][31][32]. Notably, these generally successful synthetic routes produce a considerable amount of transition metal waste (next to the inherent use of solvents) and are therefore in misalignment with the principles

• (Scheme 1f) [45][46][47]. These approaches are an elegant alternative to the transmetallation route performing without unwanted transition metal waste. Two possible direct mechanochemical pathways have been presented for the synthesis of copper(I)/NHC complexes: First, the complexes can be synthesized by

Group 13 exchange and transborylation in catalysis

• Dominic R. Willcox and
• Stephen P. Thomas

Beilstein J. Org. Chem. 2023, 19, 325–348, doi:10.3762/bjoc.19.28

• for catalysis, due to the generally higher abundance and lower toxicity of these elements. Group 13 elements have a rich catalogue of stoichiometric addition reactions to unsaturated bonds but cannot undergo the redox chemistry which underpins transition-metal catalysis. Group 13 exchange reactions

• after In‒N/B‒H exchange with HBpin gave a borylimine iron complex 110. A second hydroelementation and In‒N/B‒H exchange gave the bisborylamine 113 and regenerated the HInCl2 107 co-catalyst (Scheme 27). Conclusion Increasing concerns over the sustainability and toxicity of many transition-metal

Strategies to access the [5-8] bicyclic core encountered in the sesquiterpene, diterpene and sesterterpene series

• Cécile Alleman,
• Charlène Gadais,
• Laurent Legentil and
• François-Hugues Porée

Beilstein J. Org. Chem. 2023, 19, 245–281, doi:10.3762/bjoc.19.23

Total synthesis of insect sex pheromones: recent improvements based on iron-mediated cross-coupling chemistry

• Eric Gayon,
• Guillaume Lefèvre,
• Olivier Guerret,
• Adrien Tintar and
• Pablo Chourreu

Beilstein J. Org. Chem. 2023, 19, 158–166, doi:10.3762/bjoc.19.15

• to overall processes with a low atom economy, generating a significant amount of chemical waste, and which can be expensive when noble metals such as palladium salts are required (Scheme 1). The high efficiency of transition-metal-catalyzed cross-coupling methods in C–C bond formation processes

1,4-Dithianes: attractive C2-building blocks for the synthesis of complex molecular architectures

• Bram Ryckaert,
• Ellen Demeyere,
• Frederick Degroote,
• Hilde Janssens and
• Johan M. Winne

Beilstein J. Org. Chem. 2023, 19, 115–132, doi:10.3762/bjoc.19.12

• untapped potential in this area of research, and expect the utility of these building blocks to grow in the coming years. In particular, the recently established options to elaborate and functionalize 1,4-dithianes using mild transition-metal-catalyzed couplings, and their use in cycloaddition reactions

Practical synthesis of isocoumarins via Rh(III)-catalyzed C–H activation/annulation cascade

• Qian-Ci Gao,
• Yi-Fei Li,
• Jun Xuan and
• Xiao-Qiang Hu

Beilstein J. Org. Chem. 2023, 19, 100–106, doi:10.3762/bjoc.19.10

• of 1,2-difunctionalized arenes with alkynes or carbon monoxide (Scheme 1b, III) [13][14][15][16], have been widely applied for the assembly of isocoumarins over the past decades. Recently, the transition-metal-catalyzed ortho C–H activation/annulation of benzoic acids has emerged as an attractive

• , delivering a variety of structurally diverse isocoumarins in an efficient manner (3aa–qa, 43–82%). It is worth mentioning that the tolerance of halogen substituents (Cl, Br and I) may open up a new opportunity for further transition-metal-catalyzed cross-coupling reactions. Sensitive groups, such as ester

• , the reaction of the isocoumarin 3ia with p-toluenesulfonyl hydrazide proceeded smoothly to deliver hydrazone 5 in 66% yield (Scheme 4b, right). Of note, oxime and hydrazone compounds are versatile synthetic building blocks, which have been widely applied in transition-metal-catalyzed cross-coupling

NaI/PPh₃-catalyzed visible-light-mediated decarboxylative radical cascade cyclization of N-arylacrylamides for the efficient synthesis of quaternary oxindoles

• Dan Liu,
• Yue Zhao and
• Frederic W. Patureau

Beilstein J. Org. Chem. 2023, 19, 57–65, doi:10.3762/bjoc.19.5

• is mediated by visible light irradiation. A wide range of substrates bearing different substituents and derived from ubiquitous carboxylic acids, including α-amino acids, were synthesized and examined under this very mild, efficient, and cost effective transition-metal-free synthetic method. These

• limited substrate scopes (Scheme 1a). With the rapid development of sustainable chemistry, developing low-cost and transition-metal-free photocatalytic methods has become a strategic priority. In 2019 [54], the groups of Fu and Shang pioneered the photocatalytic decarboxylative alkylation of silyl enol

• decarboxylative radical cascade cyclization of N-arylacrylamides with various redox-active esters derived from common and/or important carboxylic acids under mild conditions. Complementary to traditional transition metal photocatalysis and organo-photocatalysis [85], the readily available and inexpensive NaI/PPh3

Improving the accuracy of ³¹P NMR chemical shift calculations by use of scaling methods

• William H. Hersh and
• Tsz-Yeung Chan

Beilstein J. Org. Chem. 2023, 19, 36–56, doi:10.3762/bjoc.19.4

• ] and polyoxometalates [33]. More recently, DFT methods have been applied to transition metal phosphorus complexes that cover a wide range of chemical shifts [34][35] using methods related to what we will describe here, but such studies are beyond the scope of this paper and typically focus on one metal

Combining the best of both worlds: radical-based divergent total synthesis

• Kyriaki Gennaiou,
• Antonios Kelesidis,
• Maria Kourgiantaki and
• Alexandros L. Zografos

Beilstein J. Org. Chem. 2023, 19, 1–26, doi:10.3762/bjoc.19.1

• reactions of transition metal hydrides (Fe, Co, Mn, etc) with alkenes (e.g., Mukaiyama hydration) [20]. The last decade saw the development of milder methods for generating carbon-centered radicals as the advancement of their reactivity in cross-coupling reactions, the concept of photoredox catalysis [21

Redox-active molecules as organocatalysts for selective oxidative transformations – an unperceived organocatalysis field

• Elena R. Lopat’eva,
• Igor B. Krylov,
• Dmitry A. Lapshin and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2022, 18, 1672–1695, doi:10.3762/bjoc.18.179

• oxidative coupling processes (also known as cross-dehydrogenative coupling), as well as late-stage CH-functionalization. Oxidation processes are recognized as a challenge in fine organic synthesis technology [10][11] due to selectivity problems and frequent need for toxic transition metal salts and

• SelectfluorTM (Scheme 8). As was mentioned above, the N-hydroxyimide-organocatalyzed aerobic CH-oxidation at room temperature requires transition metal salts as co-catalysts. Transition metal salts are undesirable due to potential contamination of the target products or the inactivation of the catalytic system

• in the case of chelating substrates [80]. In order to avoid the usage of transition metal salts, metal-free oxidative systems for the generation of imide-N-oxyl radicals were proposed. In the majority of such systems, an N-hydroxyimide undergoes single-electron oxidation photochemically by a

Functionalization of imidazole N-oxide: a recent discovery in organic transformations

• Koustav Singha,
• Imran Habib and
• Mossaraf Hossain

Beilstein J. Org. Chem. 2022, 18, 1575–1588, doi:10.3762/bjoc.18.168

• substitution reactions Metal-free coupling reaction through nucleophilic substitution of H-atom (SNH) In 2020, a C–H/C–Li coupling reaction between 2H-imidazole 1-oxides and pentafluorophenyllithium under transition metal-free conditions was reported by Timofey D. Moseev and co-workers [17]. The reaction

• provide the targeted products 11a–h. In the next year (2021), the same authors suggested another fascinating deoxygenative transition-metal-free SNH coupling reaction procedure of 2H-imidazole 1-oxides with polyphenols [10]. This process is convenient for producing bioactive bifunctional compounds

• . Transition-metal-free three-component reactions, cycloaddition reaction methodology and nucleophilic addition reaction, mainly these three types of reaction methodologies can be found in the literature reports. The approaches were greener and the reaction conditions were milder or not harsh in most of the

A facile approach to spiro[dihydrofuran-2,3'-oxindoles] via formal [4 + 1] annulation reaction of fused 1H-pyrrole-2,3-diones with diazooxindoles

• Pavel A. Topanov,
• Anna A. Maslivets,
• Maksim V. Dmitriev,
• Irina V. Mashevskaya,
• Yurii V. Shklyaev and
• Andrey N. Maslivets

Beilstein J. Org. Chem. 2022, 18, 1532–1538, doi:10.3762/bjoc.18.162

• compounds to molecules containing an enone fragment. Cycloaddition reactions involving diazo and enone moieties are usually carried out using transition-metal catalysis [18][19][20], with catalyst-free reactions being carried out only with the participation of reactive unsubstituted diazomethane [21][22][23

An alternative C–P cross-coupling route for the synthesis of novel V-shaped aryldiphosphonic acids

• Stephen J. I. Shearan,
• Enrico Andreoli and
• Marco Taddei

Beilstein J. Org. Chem. 2022, 18, 1518–1523, doi:10.3762/bjoc.18.160

• order of addition of reactants to perform the transition-metal-catalyzed C–P cross-coupling reaction, often referred to as the Tavs reaction, employing NiCl2 as a pre-catalyst in the phosphonylation of aryl bromide substrates using triisopropyl phosphite. This new method was employed in the synthesis of

• three novel aryl diphosphonate esters which were subsequently transformed to phosphonic acids through silylation and hydrolysis. Keywords: arylphosphonic acids; cross-coupling reaction; phosphonate esters; transition-metal catalysis; Introduction Phosphonates and phosphonic acids are a very

• often either non-porous or have low porosity and have little to no long-range order. The idea here was that the V-shaped linkers, as well as different substituents attached to nitrogen, could potentially force a non-layered porous structure. Conventionally, the transition-metal-catalyzed C–P cross

Molecular and macromolecular electrochemistry: synthesis, mechanism, and redox properties

• Shinsuke Inagi and
• Mahito Atobe

Beilstein J. Org. Chem. 2022, 18, 1505–1506, doi:10.3762/bjoc.18.158

• , polymer electrolyte membrane electrolysis technology, and new methods coupled with photoredox catalysts or transition metal catalysis, resulting in remarkable progress in organic electrosynthetic processes. Theoretical calculations have also led to a better understanding of the electron transfer behavior

1,4,6,10-Tetraazaadamantanes (TAADs) with N-amino groups: synthesis and formation of boron chelates and host–guest complexes

• Artem N. Semakin,
• Ivan S. Golovanov,
• Yulia V. Nelyubina and
• Alexey Yu. Sukhorukov

Beilstein J. Org. Chem. 2022, 18, 1424–1434, doi:10.3762/bjoc.18.148

• Tripodal molecules are widely used as chelating ligands for transition metal catalysis [1][2][3], sensors for ions and small molecules [4][5], reagents for surface grafting [6], building blocks for the construction of supramolecular structures [7], polycyclic cage molecules [8], and porous materials [9

Synthesis of meso-pyrrole-substituted corroles by condensation of 1,9-diformyldipyrromethanes with pyrrole

• Baris Temelli and
• Pinar Kapci

Beilstein J. Org. Chem. 2022, 18, 1403–1409, doi:10.3762/bjoc.18.145

• porphyrins, are tetrapyrrolic aromatic compounds, with the lack of one meso-carbon atom on the macrocycle [1][2][3][4]. This feature supplies a smaller ring cavity than in the case of porphyrins, three NH in the core, and coordination ability with high-valence transition metal ions. It is noteworthy that

Synthesis and electrochemical properties of 3,4,5-tris(chlorophenyl)-1,2-diphosphaferrocenes

• Almaz A. Zagidullin,
• Farida F. Akhmatkhanova,
• Mikhail N. Khrizanforov,
• Robert R. Fayzullin,
• Tatiana P. Gerasimova,
• Ilya A. Bezkishko and
• Vasili A. Miluykov

Beilstein J. Org. Chem. 2022, 18, 1338–1345, doi:10.3762/bjoc.18.139

• transition metal-catalyzed cross-coupling reactions broadly used for the preparation of different diarylacetylenes and, rarely, bis(chlorophenyl)acetylenes. Next, starting substituted benzaldehydes were treated with an excess of SOCl2 for 24 h at 25 °C. Corresponding substituted benzal chlorides 4 were

B–N/B–H Transborylation: borane-catalysed nitrile hydroboration

• Filip Meger,
• Alexander C. W. Kwok,
• Franziska Gilch,
• Dominic R. Willcox,
• Alex J. Hendy,
• Kieran Nicholson,
• Andrew D. Bage,
• Thomas Langer,
• Thomas A. Hunt and
• Stephen P. Thomas

Beilstein J. Org. Chem. 2022, 18, 1332–1337, doi:10.3762/bjoc.18.138

• relies upon stoichiometric reagents or transition-metal catalysis. Herein, a borane-catalysed hydroboration of nitriles to give primary amines is reported. Good yields (48–95%) and chemoselectivity (e.g., ester, nitro, sulfone) were observed. DFT calculations and mechanistic studies support the proposal

• research into the development of new catalytic methodologies, specifically those that use Earth-abundant and low toxicity elements, as an alternative to transition-metal catalysis [9][10]. Using metal-free catalytic systems, including boron-based catalysts, circumvents some of the issues associated with

Ionic multiresonant thermally activated delayed fluorescence emitters for light emitting electrochemical cells

• Merve Karaman,
• Abhishek Kumar Gupta,
• Subeesh Madayanad Suresh,
• Tomas Matulaitis,
• Lorenzo Mardegan,
• Daniel Tordera,
• Henk J. Bolink,
• Sen Wu,
• Stuart Warriner,
• Ifor D. Samuel and
• Eli Zysman-Colman

Beilstein J. Org. Chem. 2022, 18, 1311–1321, doi:10.3762/bjoc.18.136

• and emission takes place within the intrinsic region [2][3][4][5][6]. Two families of widely investigated emitters for LEECs are ionic transition metal complexes (iTMCs) [7][8][9][10] and conjugated polymers (CPs) [4]. From the early use of ruthenium(II) complexes, a significant amount of research has

Derivatives of benzo-1,4-thiazine-3-carboxylic acid and the corresponding amino acid conjugates

• Péter Kisszékelyi,
• Tibor Peňaška,
• Klára Stankovianska,
• Mária Mečiarová and
• Radovan Šebesta

Beilstein J. Org. Chem. 2022, 18, 1195–1202, doi:10.3762/bjoc.18.124

• a reversible acidochromic behavior [30]. Zhao et al. demonstrated a three-component transition-metal-free aerobic method using a KI/DMSO/O2 system for the facile generation of iminobenzo-1,4-thiazines in moderate to good yield [31]. 3,4-Dihydro-2H-benzo-1,4-thiazine derivatives 6 were also

Heterogeneous metallaphotoredox catalysis in a continuous-flow packed-bed reactor

• Wei-Hsin Hsu,
• Susanne Reischauer,
• Peter H. Seeberger,
• Bartholomäus Pieber and
• Dario Cambié

Beilstein J. Org. Chem. 2022, 18, 1123–1130, doi:10.3762/bjoc.18.115

• catalytic approaches [9]. Especially the combination with other transition metal catalysts (metallaphotoredox catalysis), such as nickel complexes, resulted in a vast number of new methods to achieve cross-couplings under mild conditions [10]. However, the conditions of these methods are often hard to

• development of several strategies to immobilize transition-metal photocatalysts [22]. In the case of flow-metallaphotoredox catalysis packed-bed reactors were not applied to date. This is likely because these reactions are mainly carried out using homogeneous catalysis. Several studies have shown that the

Synthesis of N-phenyl- and N-thiazolyl-1H-indazoles by copper-catalyzed intramolecular N-arylation of ortho-chlorinated arylhydrazones

• Yara Cristina Marchioro Barbosa,
• Guilherme Caneppele Paveglio,
• Claudio Martin Pereira de Pereira,
• Sidnei Moura,
• Cristiane Storck Schwalm,
• Gleison Antonio Casagrande and
• Lucas Pizzuti

Beilstein J. Org. Chem. 2022, 18, 1079–1087, doi:10.3762/bjoc.18.110

• reaction of hydrazones and p-benzoquinones [16], and Co3+/Cu2+-catalyzed C−N/N−N coupling of imidates with anthranils as both aminating reagents and organic oxidants [17]. Additional established routes to 1H-indazoles comprise transition metal‐catalyzed [18][19][20] and metal-free [21][22] intramolecular

Electrochemical formal homocoupling of sec-alcohols

• Kosuke Yamamoto,
• Kazuhisa Arita,
• Masashi Shiota,
• Masami Kuriyama and
• Osamu Onomura

Beilstein J. Org. Chem. 2022, 18, 1062–1069, doi:10.3762/bjoc.18.108

• alcohol derivatives. The present transformations smoothly proceed in a simple undivided cell under constant current conditions without the use of external chemical oxidants/reductants, and transition-metal catalysts. Keywords: alcohols; dimerization; electrooxidation; electroreduction; paired

• catalytic amount of transition-metal reductants have been developed, but stoichiometric silicon electrophiles and co-reductants such as Zn were commonly required to complete the catalytic cycle [14]. More recently, visible light-mediated pinacol coupling reactions have been disclosed by several groups [15

• ][16][17][18]. In addition to the reductive coupling of carbonyl compounds, oxidative homocoupling reactions of benzyl alcohols under transition metal- or semiconductor-based photoredox catalysis have been demonstrated as attractive approaches to access vic-1,2-diols [19][20][21][22][23

Automated grindstone chemistry: a simple and facile way for PEG-assisted stoichiometry-controlled halogenation of phenols and anilines using N-halosuccinimides

• Dharmendra Das,
• Akhil A. Bhosle,
• Amrita Chatterjee and
• Mainak Banerjee

Beilstein J. Org. Chem. 2022, 18, 999–1008, doi:10.3762/bjoc.18.100

• with N-bromosuccinimide (NBS) was carried out in toxic polar solvents (e.g., DMF), but no iodinated or chlorinated products were obtained because of the low reactivity of NIS and NCS (Scheme 1a) [24][25][26][27]. In recent time, the use of Lewis or Brønsted acids, Lewis bases, and transition-metal