Carbonylative synthesis and functionalization of indoles

• Alex De Salvo,
• Raffaella Mancuso and
• Xiao-Feng Wu

Beilstein J. Org. Chem. 2024, 20, 973–1000, doi:10.3762/bjoc.20.87

• isolated product was an indol-3-one derivative (Scheme 14). Another example for the synthesis of 3-substituted indoles was described by Hsieh and Dong [35]. They synthesized 3-arylindoles by palladium-catalyzed C–H bond amination via reduction of nitroalkenes using carbon monoxide as reducing agent. The

• palladium-catalyzed reductive N-heteroannulation. Synthesis of 3-arylindoles by palladium-catalyzed C–H bond amination via reduction of nitroalkenes. Synthesis of 2,2′-bi-1H-indoles, 2,3′-bi-1H-indoles, 3,3′-bi-1H-indoles, indolo[3,2-b]indoles, indolo[2,3-b]indoles, and 4,4′-diaza-3,3′-bi-1H-indole. Pd

Ortho-ester-substituted diaryliodonium salts enabled regioselective arylocyclization of naphthols toward 3,4-benzocoumarins

• Ke Jiang,
• Cheng Pan,
• Limin Wang,
• Hao-Yang Wang and
• Jianwei Han

Beilstein J. Org. Chem. 2024, 20, 841–851, doi:10.3762/bjoc.20.76

• advantage, facilitating the formation of two or more chemical bonds in a step-economic manner [9][10][11][12][13]. In a prior study, we reported a palladium-catalyzed efficient activation of both C–I bond and the adjacent C–H bond of diaryliodonium salts in the formation of 4,5-benzocoumarin derivatives

Advancements in hydrochlorination of alkenes

• Daniel S. Müller

Beilstein J. Org. Chem. 2024, 20, 787–814, doi:10.3762/bjoc.20.72

• ) [78]. Another advantage of the MH HAT process is that the α-C–H bond in the corresponding radical is comparatively stable, whereas a carbocation has superacidic α-C–H bonds with a pKa of ≈ −17 [79]. Therefore, polar hydrochlorination reactions are in competition with elimination reactions which is not

Regioselective quinazoline C2 modifications through the azide–tetrazole tautomeric equilibrium

• Dāgs Dāvis Līpiņš,
• Andris Jeminejs,
• Una Ušacka,
• Anatoly Mishnev,
• Māris Turks and
• Irina Novosjolova

Beilstein J. Org. Chem. 2024, 20, 675–683, doi:10.3762/bjoc.20.61

• position of quinazolines requires longer time, higher temperatures, and sometimes the use of expensive transition-metal catalysts [12]. A selective C2 modification can be achieved by using 2-chloroquinazolines IV, where the C4 position is blocked by an unreactive C–C or C–H bond (Scheme 1). Cyclization

Mono or double Pd-catalyzed C–H bond functionalization for the annulative π-extension of 1,8-dibromonaphthalene: a one pot access to fluoranthene derivatives

• Nahed Ketata,
• Linhao Liu,
• Ridha Ben Salem and
• Henri Doucet

Beilstein J. Org. Chem. 2024, 20, 427–435, doi:10.3762/bjoc.20.37

• palladium-catalyzed direct intermolecular arylation, followed by a direct intramolecular arylation step. As the C–H bond activation of several benzene derivatives remains very challenging, the preparation of fluoranthenes from 1,8-dibromonaphthalene via Suzuki coupling followed by intramolecular C–H

• activation has also been investigated to provide a complementary method. Using the most appropriate synthetic route and substrates, it is possible to introduce the desired functional groups at positions 7–10 on fluoranthenes. Keywords: catalysis; C–H bond functionalization; direct arylation; fluoranthenes

• using commercially available substrates and allowing the regioselective introduction of functional groups at the desired positions is still needed. By using Pd-catalyzed double C–H bond functionalization of activated arenes, such as (poly)fluoroarenes, or by combining a palladium-catalyzed

Substitution reactions in the acenaphthene analog of quino[7,8-h]quinoline and an unusual synthesis of the corresponding acenaphthylenes by tele-elimination

• Ekaterina V. Kolupaeva,
• Narek A. Dzhangiryan,
• Alexander F. Pozharskii,
• Oleg P. Demidov and
• Valery A. Ozeryanskii

Beilstein J. Org. Chem. 2024, 20, 243–253, doi:10.3762/bjoc.20.24

• of quinoquinolines, their planar structure, and very easy coordination to acidic and electrophilic sites (including water [15][22] or the C–H bond of chloroform [11]) almost always lead to co-crystallization. For example, there is no such crystallographic information for quinoquinoline 3 itself. In

N-Boc-α-diazo glutarimide as efficient reagent for assembling N-heterocycle-glutarimide diads via Rh(II)-catalyzed N–H insertion reaction

• Grigory Kantin,
• Pavel Golubev,
• Alexander Sapegin,
• Alexander Bunev and
• Dmitry Dar’in

Beilstein J. Org. Chem. 2023, 19, 1841–1848, doi:10.3762/bjoc.19.136

• catalyst for obtaining the product of insertion into the NH bond of the heterocycle. An effort to obtain the N–H insertion product with dibenzoazepine proved fruitless. Instead, the product of insertion into the C–H bond of the activated benzene ring (9z) was isolated in moderate yield. The chemo- and

C–H bond functionalization: recent discoveries and future directions

• Indranil Chatterjee

Beilstein J. Org. Chem. 2023, 19, 1568–1569, doi:10.3762/bjoc.19.114

• Indranil Chatterjee Department of Chemistry, Indian Institute of Technology Ropar, Nangal Road, Rupnagar, Punjab 140001, India 10.3762/bjoc.19.114 Keywords: C–H bond functionalization; The process of C–H bond functionalization can be defined as the replacement of an activated or nonactivated C−H

• the abstraction of intramolecular hydrogen atoms. Radical chemistry is a viable alternative to the two-electron process, involving C–H bond functionalization in the absence of any ligand and using low-cost redox-active metals (Fe, Cu, Mn, etc.) rather than heavy metals (Rh, Ir, etc.). Although radical

• its combination with organometallic chemistry for site-selective C−H bond functionalization [3][4]. Recent years have witnessed many viable strategies for the synthesis of complex targets utilizing photoredox catalysis, electroorganic catalysis, Lewis acid catalysis, and transition-metal-free

Lewis acid-promoted direct synthesis of isoxazole derivatives

• Dengxu Qiu,
• Chenhui Jiang,
• Pan Gao and
• Yu Yuan

Beilstein J. Org. Chem. 2023, 19, 1562–1567, doi:10.3762/bjoc.19.113

• developed to prepare isoxazole derivatives [10][11][12][13]. However, most of the starting materials for these methods are oximes and hydroximinoyl chlorides [4][13][14][15]. Recently, the sp3 C–H bond functional group transformation of 2-methylquinoline derivatives into isoxazole derivatives has been

• the Lewis acid to realize the sp3 C–H-bond activation of nitrogen heterocycles to synthesize isoxazole derivatives. Results and Discussion At the outset of this study, we chose the reaction of 2-methylquinoline (2a) with phenylacetylene (1a) in the presence of AlCl3 (3 equiv) and sodium nitrite (10

• oxide E [23], which can be converted to the desired isoxazole with 1a through a 1,3-dipolar cycloaddition. Conclusion In conclusion, we have developed an efficient and concise synthesis of isoxazole nitrogen heterocycles by direct C–H-bond activation of methyl heteroaromatics. The method avoids using

N-Sulfenylsuccinimide/phthalimide: an alternative sulfenylating reagent in organic transformations

• Fatemeh Doraghi,
• Seyedeh Pegah Aledavoud,
• Mehdi Ghanbarlou,
• Bagher Larijani and
• Mohammad Mahdavi

Beilstein J. Org. Chem. 2023, 19, 1471–1502, doi:10.3762/bjoc.19.106

• this work. In 2018, Anbarasan and Chaitanya developed an efficient approach for the C–H bond functionalization of aryl compounds containing a directing group using N-(thioaryl)phthalimides 14 in the presence of a palladium catalyst (Scheme 15) [53]. The thiolation occurred in the presence of Pd(OAc)2

• substitution to provide C2,C3-disulfenylated product 66 (Scheme 28). In the same year, Sutherland and Dodds disclosed a protocol for the C–H bond thioarylation of electron-rich arenes 4 like anisoles, acetanilides, phenols, and N-heterocycles in the presence of Fe(III) Lewis acid and ionic liquid [BMIM]NTf2 as

Non-noble metal-catalyzed cross-dehydrogenation coupling (CDC) involving ether α-C(sp³)–H to construct C–C bonds

• Hui Yu and
• Feng Xu

Beilstein J. Org. Chem. 2023, 19, 1259–1288, doi:10.3762/bjoc.19.94

• become a major strategy for ether functionalization. This review covers C–H/C–H cross-coupling reactions of ether derivatives with various C–H bond substrates via non-noble metal catalysts (Fe, Cu, Co, Mn, Ni, Zn, Y, Sc, In, Ag). We discuss advances achieved in these CDC reactions and hope to attract

• overcome the shortcomings of the above coupling reactions, organic chemists have envisaged the construction of C–C bonds directly through C–H bond activation [5]. Fortunately, scientists have used various transition metals as catalysts to realize the activation of various types of C–H bonds, and have

• ether α-C–H bond. In the presence of Cu(II), the C(sp2)–C(sp3) coupling of pyridine N-oxides and coumarins with cyclic ethers could be achieved under mild conditions (Scheme 13) [63][64]. These reactions do not all follow the reaction mechanism of the oxidative olefination of simple ethers. The role of

Radical ligand transfer: a general strategy for radical functionalization

• David T. Nemoto Jr,
• Kang-Jie Bian,
• Shih-Chieh Kao and
• Julian G. West

Beilstein J. Org. Chem. 2023, 19, 1225–1233, doi:10.3762/bjoc.19.90

• alkyl C–H bond to a high valent iron oxo species, resulting in formation of iron hydroxo and alkyl radical intermediates [15]. Subsequent RLT of the hydroxo ligand to the alkyl radical produces a hydroxylated product, allowing for metabolism and excretion of previously diverse bioactive compounds

• enzymes consists of HAT on a C–H bond, followed by RLT with a hydroxy ligand. II: Kochi reported the oxidation of alkyl radicals through LMCT of copper(II) chloride and subsequent radical chlorine ligand transfer [26]. 1-Cyclohexene was also reported to be oxidized to the vicinal dichlorinated product

Photoredox catalysis harvesting multiple photon or electrochemical energies

• Mattia Lepori,
• Simon Schmid and
• Joshua P. Barham

Beilstein J. Org. Chem. 2023, 19, 1055–1145, doi:10.3762/bjoc.19.81

Aromatic C–H bond functionalization through organocatalyzed asymmetric intermolecular aza-Friedel–Crafts reaction: a recent update

• Anup Biswas

Beilstein J. Org. Chem. 2023, 19, 956–981, doi:10.3762/bjoc.19.72

• bond is thermodynamically stable and possesses a high bond dissociation energy opposing the bond to easy chemical transformation. Therefore, harsh reaction conditions and the necessity of an external activator like catalysts are common prerequisites for processes involving C–H bond breaking. Among

• different types of C–H bonds, an aromatic C–H bond is even more inert rendering this type of bond functionalization more difficult. Herewith the term “bond functionalization” is defined as the cleavage of an existing bond with substitution by another bond. Aromatic C–H bond functionalizations have gained

• considerable attention by organic chemists because of the strategic importance of this process as well as the ability to synthesize functionalized aromatic molecules in a straightforward way. Many organic name reactions have been discovered utilizing the C–H bond functionalization concept [1]. Metals were

Photoredox catalysis enabling decarboxylative radical cyclization of γ,γ-dimethylallyltryptophan (DMAT) derivatives: formal synthesis of 6,7-secoagroclavine

• Alessio Regni,
• Francesca Bartoccini and
• Giovanni Piersanti

Beilstein J. Org. Chem. 2023, 19, 918–927, doi:10.3762/bjoc.19.70

• Hz, 1H)], strongly indicating that this product is not the desired structure 6’ but the eight-membered cycloalkene structure 6, shown in Scheme 2. Based on these results and previous reports on the benzylic and allylic C–H bond functionalization enabled by metallaphotoredox catalysis [86], we propose

• a tentative mechanism (Figure 2). First, the radical cation I was generated via the oxidation of indole 5 by the excited Ir-based photocatalyst, followed by sequential regioselective proton transfer on the benzylic dimethylallyl unit C–H bond of the C4 side-chain, thereby generating II. Here, the

Pyridine C(sp²)–H bond functionalization under transition-metal and rare earth metal catalysis

• Haritha Sindhe,
• Malladi Mounika Reddy,
• Karthikeyan Rajkumar,
• Akshay Kamble,
• Amardeep Singh,
• Anand Kumar and
• Satyasheel Sharma

Beilstein J. Org. Chem. 2023, 19, 820–863, doi:10.3762/bjoc.19.62

• rare earth metal-catalyzed reactions have flourished over the past two decades in the development of functionalized organic molecules of concern. In this review, we discuss recent achievements in the transition-metal and rare earth metal-catalyzed C–H bond functionalization of pyridine and look into

• functionalize a C–H bond in pyridine with traditional chemical transformations. On the other hand, intriguing developments have been made for the functionalization of inert C–H bonds in organic synthesis during the past two decades. In this regard, the transition-metal-catalyzed C–H functionalization has made

• . Review C–H Alkylation of pyridine The C–H bond is the backbone of an organic molecule and the conversion of a C–H bond to a C–X bond (X = carbon or heteroatom) forms the basis in organic synthesis. The functionalization of C–H bonds is challenging due to a large kinetic barrier for C–H bond cleavage and

Enolates ambushed – asymmetric tandem conjugate addition and subsequent enolate trapping with conventional and less traditional electrophiles

• Péter Kisszékelyi and
• Radovan Šebesta

Beilstein J. Org. Chem. 2023, 19, 593–634, doi:10.3762/bjoc.19.44

• functional group tolerance with excellent stereoselectivities. In 2016, Ellman and co-workers demonstrated a Rh- or Co-catalyzed highly diastereoselective tandem C–H bond addition/aldol reaction sequence [96][97]. The C–H activation was promoted by pyridine, pyrazole, or imine directing groups, while the

Transition-metal-catalyzed domino reactions of strained bicyclic alkenes

• Austin Pounder,
• Eric Neufeld,
• Peter Myler and
• William Tam

Beilstein J. Org. Chem. 2023, 19, 487–540, doi:10.3762/bjoc.19.38

• -catalyzed [3 + 2] annulation/ring-opening/dehydration domino reaction of oxabicyclic alkenes 30 with 2-(1-methylhydrazinyl)pyridine (MHP) directed arenes 87 for the synthesis of benzo[b]fluorenones 88 (Scheme 16) [52]. C–H bond functionalization with heterobicyclic alkenes as annulation partners has

• salicylaldehydes with EWGs failed to react. The authors hypothesized the reaction mechanism begins with the association of the Rh(III) catalyst with the hydroxy group of salicylaldehyde (151a) resulting in a selective cleavage of the aldehyde C–H bond producing the rhodocycle 153 which side-on coordinates with the

• substituent trends were seen as that with the reaction with O-acetyl ketoximes. Mechanistically, the reaction begins when the Rh(III) catalyst is converted to an active Rh(III) species, by AgSbF6 and Cu(OAc)2, which oxidatively inserts into the ortho C–H bond forming 163. Migratory insertion of the alkene

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

• functionalization of C(sp2) and C(sp3) centers with SCF3, SeCF3, or OCH2CF3 groups among others, by C–H bond activation. The scope and limitations of these transformations are discussed in this review. Keywords: C–H bond activation; emergent fluorinated groups; homogeneous catalysis; organofluorine chemistry

• [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

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

• benzyl iodides was observed. Besides classical NHPI/PINO-catalyzed CH-functionalization processes, there is a significant number of works in which PINO plays the role of both the catalyst for C–H bond cleavage and the reagent intercepting the resultant C-centered radical [90]. As a rule, stoichiometric

• introduction of an electron-withdrawing acetoxy group. The DABCO cation radical is less reactive compared to quinuclidine-derived cation radicals. It was involved in the Ni-catalyzed oxidative C–C cross-coupling involving aldehyde C–H bond cleavage with the formation of acyl radicals according to the proposed

• benzylic substrates with azoles was developed [128] (Scheme 27). In the proposed mechanism DDQ participated in benzylic C–H bond cleavage. The C–N bond of the final product is formed as a result of the nucleophilic attack of azole on a benzylic cation. A two-fold molar excess of azoles was used. 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

• review paper exploring several procedures of C–H bond activation for the functionalization of N-oxides [12] and in 2019, Dongli Li and co-workers analyzed heterocyclic N-oxides with regard to their usefulness in synthesis of organic drug molecules and catalysis [13]. Many review papers have been

Simple synthesis of multi-halogenated alkenes from 2-bromo-2-chloro-1,1,1-trifluoroethane (halothane)

• Yukiko Karuo,
• Atsushi Tarui,
• Kazuyuki Sato,
• Kentaro Kawai and
• Masaaki Omote

Beilstein J. Org. Chem. 2022, 18, 1567–1574, doi:10.3762/bjoc.18.167

• for obtaining 1. The desired highly halogenated aryl alkenyl ether 2a was obtained, but the yield was unacceptably low (Table 1, entry 1). The low conversion is attributed to use of an insufficient amount of KOH, which was used as a base for deprotonation of the phenolic hydroxy group and acidic C–H

• bond between the bromine and chlorine atoms in 1. Extra KOH was added to improve deprotonation, but the yield of 2a was still low (Table 1, entries 2 and 3). Changing the solvent from THF to DME and increasing the temperature to 80 °C slightly improved the yield of 2a to 19% (Table 1, entry 4

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

• amination by oxidative C−H bond functionalizations. These methods showed significant improvement with respect to the substrate scope and reaction conditions. However, mostly they are restricted to substrates containing hydrogen [13][14], alkyl [14][15], or (substituted) phenyl moieties [14][16][17] as N

Synthetic strategies for the preparation of γ-phostams: 1,2-azaphospholidine 2-oxides and 1,2-azaphospholine 2-oxides

• Jiaxi Xu

Beilstein J. Org. Chem. 2022, 18, 889–915, doi:10.3762/bjoc.18.90

• method to synthesize 1,2-azaphospholidine 2-oxide derivatives 13. Arylphosphinyl azides generate arylphosphinyl nitrenes under photoirradiation. The phosphinyl nitrenes underwent an intramolecular insertion into the ortho C–H bond of the aryl group accompanied with the Curtius-like rearrangement as well

• (Scheme 5) [25]. The metal-free intramolecular oxidative C–H bond amidation of methyl and ethyl 2,6-dimethylphenylphosphonamidates 24, 26, and 28 is an interesting strategy for the synthesis of 1-methoxy/ethoxy-7-methyl-2-hydrobenzo[c][1,2]azaphosphol-3-one 1-oxide derivatives 25, 27, and 29 in

• 105 via the copper-catalyzed intramolecular carbene aromatic C–H bond insertion (Scheme 20) [44]. This is an efficient synthetic strategy for 3-benzoyl-2-ethoxy-1,3-dihydrobenzo[d][1,2]azaphosphole 2-oxides 106 through the formation of the C–C bond neighboring at the ring phosphorus atom. Synthesis

Structural basis for endoperoxide-forming oxygenases

• Takahiro Mori and
• Ikuro Abe

Beilstein J. Org. Chem. 2022, 18, 707–721, doi:10.3762/bjoc.18.71

• highly reactive Fe(IV)=O species and a succinate byproduct. This Fe(IV)=O abstracts a hydrogen atom from an aliphatic C–H bond of the substrate to generate a radical intermediate. When the enzyme catalyzes the hydroxylation reaction, the radical reacts with the Fe(III)-OH species to form a hydroxylated