One-pot double annulations to confer diastereoselective spirooxindolepyrrolothiazoles

• Juan Lu,
• Bin Yao,
• Desheng Zhan,
• Zhuo Sun,
• Yun Ji and
• Xiaofeng Zhang

Beilstein J. Org. Chem. 2022, 18, 1607–1616, doi:10.3762/bjoc.18.171

• one-pot reactions with recyclable organocatalysts [69]. Notably, we conferred K10 acid to promote the C–H activation in the synthesis of spirooxindolepyrrolidines, and used Zeolite HY catalyst to synthesize diastereoselective dispiro[oxindolepyrrolidine]s with a butterfly shape (Scheme 1A and 1B) [70

Modular synthesis of 2-furyl carbinols from 3-benzyldimethylsilylfurfural platforms relying on oxygen-assisted C–Si bond functionalization

• Sebastien Curpanen,
• Per Reichert,
• Gabriele Lupidi,
• Giovanni Poli,
• Julie Oble and
• Alejandro Perez-Luna

Beilstein J. Org. Chem. 2022, 18, 1256–1263, doi:10.3762/bjoc.18.131

• ][3]. As part of this effort, exploitation of furfural and corresponding derivatives attracts continuous attention [4][5][6][7]. In this area, we have actively investigated catalytic C–H activation reactions [8][9][10][11][12][13][14], and as part of this work, we have recently developed an iridium

Direct C–H amination reactions of arenes with N-hydroxyphthalimides catalyzed by cuprous bromide

• Dongming Zhang,
• Bin Lv,
• Pan Gao,
• Xiaodong Jia and
• Yu Yuan

Beilstein J. Org. Chem. 2022, 18, 647–652, doi:10.3762/bjoc.18.65

• decades. With the combination of C–H activation, many aminations of aryl compounds have been established [6][7][8][9][10][11][12][13][14][15][16]. However, it is necessary to introduce the directing group into the arene in most successful cases. As a good amino source, phthalimides have been widely

Recent developments and trends in the iron- and cobalt-catalyzed Sonogashira reactions

• Surendran Amrutha,
• Sankaran Radhika and
• Gopinathan Anilkumar

Beilstein J. Org. Chem. 2022, 18, 262–285, doi:10.3762/bjoc.18.31

• of the alkyl halide and C–H activation can be increased by the presence of active Lewis acid sites on the iron(III) nanoparticles. The scope for this catalytic system can be figured out by the presence of high temperature, high ligand concentration and activated ligands. Chen and co-workers

Iridium-catalyzed hydroacylation reactions of C1-substituted oxabenzonorbornadienes with salicylaldehyde: an experimental and computational study

• Angel Ho,
• Austin Pounder,
• Krish Valluru,
• Leanne D. Chen and
• William Tam

Beilstein J. Org. Chem. 2022, 18, 251–261, doi:10.3762/bjoc.18.30

• hydride, and C–C bond-forming reductive elimination. Computational results indicate the origin of regioselectivity is involved in the reductive elimination step. Keywords: C–H activation; density functional theory; hydroacylation; iridium catalysis; regioselectivity; Introduction Organic synthesis is

Ready access to 7,8-dihydroindolo[2,3-d][1]benzazepine-6(5H)-one scaffold and analogues via early-stage Fischer ring-closure reaction

• Irina Kuznetcova,
• Felix Bacher,
• Daniel Vegh,
• Hsiang-Yu Chuang and
• Vladimir B. Arion

Beilstein J. Org. Chem. 2022, 18, 143–151, doi:10.3762/bjoc.18.15

• -catalyzed norbornene-mediated C–H activation [35] failed and gave 1,4-bis(2-bromophenyl)piperazine-2,5-dione (22, Scheme 5) as the sole product in 61% yield, which to our knowledge is not documented in the literature yet. Synthetic pathway (c) started from methyl 4-(2-nitrophenyl)-3-oxobutanoate prepared in

Earth-abundant 3d transition metals on the rise in catalysis

• Nikolaos Kaplaneris and
• Lutz Ackermann

Beilstein J. Org. Chem. 2022, 18, 86–88, doi:10.3762/bjoc.18.8

• , Germany 10.3762/bjoc.18.8 Keywords: C–H activation; 3d transition metals; green chemistry; late-stage functionalization; sustainability; Transition metal catalysis has emerged as a transformative platform for the assembly of increasingly complex compounds, with enabling applications to natural product

• witnessed major momentum in metal-catalyzed C–H activation [4][5] as a more resource-economical strategy. This approach involves the efficient and selective cleavage of otherwise inert, yet omnipresent C–H bonds. This strategy avoids a variety of steps and reduces the amount of chemical waste. Very recently

Recent advances and perspectives in ruthenium-catalyzed cyanation reactions

• Thaipparambil Aneeja,
• Cheriya Mukkolakkal Abdulla Afsina,
• Padinjare Veetil Saranya and
• Gopinathan Anilkumar

Beilstein J. Org. Chem. 2022, 18, 37–52, doi:10.3762/bjoc.18.4

• cyclic amines than the aerobic oxidation system. The catalytic cycle for the hydrogen peroxide system involves the formation of the oxoruthenium species (A) and the low-valent ruthenium species (B), whereas the aerobic oxidation system includes C–H activation and a subsequent reaction with molecular

Peptide stapling by late-stage Suzuki–Miyaura cross-coupling

• Hendrik Gruß,
• Rebecca C. Feiner,
• Ridhiwan Mseya,
• David C. Schröder,
• Michał Jewgiński,
• Kristian M. Müller,
• Rafał Latajka,
• Antoine Marion and
• Norbert Sewald

Beilstein J. Org. Chem. 2022, 18, 1–12, doi:10.3762/bjoc.18.1

• 1% in proteins, but is highly conserved in binding sites on protein surfaces mediating PPI [43], it is an attractive target for the development of selective diversifications. C–H activation of the indole C2 position by Pd-catalysis allows both selective arylation [44][45][46][47][48] and formation

DABCO-promoted photocatalytic C–H functionalization of aldehydes

• Bruno Maia da Silva Santos,
• Mariana dos Santos Dupim,
• Cauê Paula de Souza,
• Thiago Messias Cardozo and
• Fernanda Gadini Finelli

Beilstein J. Org. Chem. 2021, 17, 2959–2967, doi:10.3762/bjoc.17.205

• strategy for aldehyde C–H activation. The acyl radicals generated in this step were arylated with aryl bromides through a well stablished nickel cross-coupling methodology, leading to a variety of interesting aryl ketones in good yields. We also performed computational calculations to shine light in the

• interchanging steps, often required in traditional synthetic methodologies [1][2]. The development of photocatalysis enabled inexpensive access to C–H activation methodologies under mild conditions, with hydrogen atom transfer (HAT) reactions standing out as a main strategy [1][3][4]. The hydrogen abstractor is

Iron-catalyzed domino coupling reactions of π-systems

• Austin Pounder and
• William Tam

Beilstein J. Org. Chem. 2021, 17, 2848–2893, doi:10.3762/bjoc.17.196

• significant development over the past 10 years. First achieved by Li and co-workers in 2007 [44], cross-dehydrogenative-coupling (CDC) reactions offer a highly atom economic approach to carbon–carbon (C–C) and carbon–heteroatom (C–X) bond formation via C–H activation [45][46]. Generally speaking, C–C bond

Recent advances in the asymmetric phosphoric acid-catalyzed synthesis of axially chiral compounds

• Alemayehu Gashaw Woldegiorgis and
• Xufeng Lin

Beilstein J. Org. Chem. 2021, 17, 2729–2764, doi:10.3762/bjoc.17.185

• aryl–aryl cross-coupling using various transition-metal catalysts has rarely been successful for the enantioselective construction of hindered biaryls [39] due to the discord between the temperature tolerance of the rotational axis and the high temperature required for C–H activation and suffered from

• be prepared by asymmetric C–H activation. The C–H activation or functionalization can be achieved by a metal-catalyzed chiral phosphoric acid ligand-assisted method, which offers distinct possibilities to provide various chiral biaryl compounds by changing different directing groups (DGs) [46]. Since

• 16 via β-H elimination using (S)-CPA 4 as a ligand (Scheme 7) [51]. The directing group (NH2) facilitated the C–H activation on the other aromatic ring and ensured its coordination with Pd to form palladacycle I-2 to restrict bond rotations and promote exclusive allylic selectivity via β-H1

Copper-catalyzed monoselective C–H amination of ferrocenes with alkylamines

• Zhen-Sheng Jia,
• Qiang Yue,
• Ya Li,
• Xue-Tao Xu,
• Kun Zhang and
• Bing-Feng Shi

Beilstein J. Org. Chem. 2021, 17, 2488–2495, doi:10.3762/bjoc.17.165

• the directing group could be removed easily under basic conditions. Keywords: amination; C–H activation; copper; ferrocene; mono-selectivity; Introduction Ferrocene-based compounds have broad applications from asymmetric catalysis to medicinal discovery [1][2][3][4][5][6][7][8]. Therefore, the

• preparation of ferrocene–drug conjugates effectively. Mechanistic studies indicated that the C–H activation step was the rate-determining step. 3d-Transition-metal-catalyzed C–H functionalization to access functionalized ferrocenes. Scope of ferrocenes with morpholine. Scope of various amines with 1a

Photoredox catalysis in nickel-catalyzed C–H functionalization

• Lusina Mantry,
• Rajaram Maayuri,
• Vikash Kumar and
• Parthasarathy Gandeepan

Beilstein J. Org. Chem. 2021, 17, 2209–2259, doi:10.3762/bjoc.17.143

• developments in the field of photoredox nickel-catalyzed C‒H functionalization reactions with a range of applications until summer 2021. Keywords: C–H activation; functionalization; nickel; photocatalysts; photoredox; visible light; Introduction During the last decades, transition-metal-catalyzed

• ]. In this review, we highlight the developments in C–H activation enabled by nickel photocatalysis. Review Arylation The arylation of C(sp3)‒H bonds constitutes a potential tool for the rapid diversification of simple organic molecules into valuable scaffolds [48][49][50][51][52]. In 2014, Doyle

• challenging operation in organic synthesis. While significant advances had been accomplished with (hetero)aromatic C(sp2)–H alkylations [79][80][81], examples for C(sp3)–C(sp3) couplings through C–H activation are scarce [82][83][84]. In this context, a synergistic combination of photoredox catalysis and

Recent advances in the syntheses of anthracene derivatives

• Giovanni S. Baviera and
• Paulo M. Donate

Beilstein J. Org. Chem. 2021, 17, 2028–2050, doi:10.3762/bjoc.17.131

• anthracene derivatives 33. The strategy involved a palladium(II)-catalyzed tandem transformation with diphenyl carboxylic acids 31 and acrylates 32 (Scheme 7) [41]. This new methodology involved a carboxyl-directed C–H alkenylation, a carboxyl-directed secondary C–H activation, an intramolecular C–C-bond

• activation In 2009, Liang et al. reported an efficient and highly regioselective route to construct substituted tetracyclic benz[a]anthracene derivatives 115 (Scheme 26) [60]. For this purpose, the authors developed an efficient palladium-catalyzed tandem C–H activation/bis-cyclization reaction of

• anthracenes from a bifunctional organomagnesium alkoxide. Palladium-catalyzed tandem C–H activation/bis-cyclization of propargylic carbonates. Ruthenium-catalyzed C–H arylation of acetophenone derivatives with arenediboronates. Pd-catalyzed intramolecular cyclization of (Z,Z)-p-styrylstilbene derivatives

On the application of 3d metals for C–H activation toward bioactive compounds: The key step for the synthesis of silver bullets

• Renato L. Carvalho,
• Amanda S. de Miranda,
• Mateus P. Nunes,
• Roberto S. Gomes,
• Guilherme A. M. Jardim and
• Eufrânio N. da Silva Júnior

Beilstein J. Org. Chem. 2021, 17, 1849–1938, doi:10.3762/bjoc.17.126

• active molecules can be obtained through C–H activation processes. However, the use of expensive and not readily accessible catalysts complicates the process of pharmacological application of these compounds. A plausible way to overcome this issue is developing and using cheaper, more accessible, and

• equally effective catalysts. First-row transition (3d) metals have shown to be important catalysts in this matter. This review summarizes the use of 3d metal catalysts in C–H activation processes to obtain potentially (or proved) biologically active compounds. Keywords: bioactive compounds; C–H

• catalysts for C–H activation processes deserves a better exploration. This review compilates the application of 3d metals as catalysts for C–H activation processes to obtain biologically active compounds or building blocks applied in the synthesis of molecules with known biological effects. Review Scandium

Sustainable manganese catalysis for late-stage C–H functionalization of bioactive structural motifs

• Jongwoo Son

Beilstein J. Org. Chem. 2021, 17, 1733–1751, doi:10.3762/bjoc.17.122

• 31n, regarded as a potentially viable peptide-based biosensor. Manganese-catalyzed inter- and intramolecular C–H alkenylations Manganese(I)-catalyzed C–H alkenylation of 2-phenylpyridines or N-pyridinylindoles with alkynes is characterized by proximity-induced C–H activation through chelation

A recent overview on the synthesis of 1,4,5-trisubstituted 1,2,3-triazoles

• Pezhman Shiri,
• Ali Mohammad Amani and
• Thomas Mayer-Gall

Beilstein J. Org. Chem. 2021, 17, 1600–1628, doi:10.3762/bjoc.17.114

• corresponding product under the standard conditions, denoting that the reaction did not include the sequence of CuAAC followed by C–H activation. According to these facts, the reaction mechanism may be as below. First, the copper(I)-substituted acetylide 78 was generated via the reaction of the copper source

• methodology for aerobic C–H activation; ii) PEG as green and recyclable reaction medium; and iii) a reusable palladium catalyst complex [65]. Fully functionalized 1,2,3-triazolo-fused chromenes 162, 164, and 166 were regioselectively prepared in moderate yield. The isoindoline-fused triazoles 164 were

Copper-mediated oxidative C−H/N−H activations with alkynes by removable hydrazides

• Feng Xiong,
• Bo Li,
• Chenrui Yang,
• Liang Zou,
• Wenbo Ma,
• Linghui Gu,
• Ruhuai Mei and
• Lutz Ackermann

Beilstein J. Org. Chem. 2021, 17, 1591–1599, doi:10.3762/bjoc.17.113

• the natural abundance and versatile reactivity. Early examples of copper-promoted C−H activation of 2-arylpyridines were disclosed by Yu et al. [12] and Chatami et al. [13] independently. Inspired by these studies, various copper-induced C−H functionalizations, such as arylations, alkynylations

• -catalyzed C−H activations with the MHP auxiliary [41][42][43][44]. In continuation of studies on sustainable 3d transition metal-catalyzed C−H activation [41][42][43][44][45][46][47][48][49], we have now discovered a robust copper-promoted oxidative C−H/N−H functionalization with terminal alkynes (Figure 1d

• Discussion We initiated our investigation by utilizing benzhydrazide 1a and ethynylbenzene (2a) as the standard substrates (Table 1). After preliminary solvent optimization, we discovered that the desired ortho-selective C−H activation occurred efficiently by the treatment of hydrazide 1a with terminal

Methodologies for the synthesis of quaternary carbon centers via hydroalkylation of unactivated olefins: twenty years of advances

• Thiago S. Silva and
• Fernando Coelho

Beilstein J. Org. Chem. 2021, 17, 1565–1590, doi:10.3762/bjoc.17.112

• suggested that iridium serves as a π-Lewis acid (although one could propose a C–H activation pathway) that activates the olefin by coordination due to the correlation observed between the nature of the Ir counterion and the reaction yields. Radical-based approaches Olefin hydroalkylation via metal hydride

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

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. Keywords: C–H activation; energy transfer; fluorination; photocatalysis; photosensitization; visible light; Review 1 Introduction 1.1 Importance of direct C–H fluorination/trifluoromethylation and photosensitization in organic synthesis 1.1.1 Importance of fluorine atoms in organic molecules

• ][119][120][121][122]. There are many approaches to photosensitized fluorination that do not involve direct C–H activation, which are reviewed elsewhere [123][124][125], such as C–C bond fragmentation/C–F bond formation [126], aminofluorination of cyclopropanes [127] and decarboxylative fluorination

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

• catalytic system is extremely appealing. In that perspective, the scope of this review aims to present innovative reactions combining C–H activation and visible-light induced photocatalysis. Keywords: C–H activation; C–H functionalization; dual catalysis; photoredox catalysis; radical chemistry

• –H activations, visible-light-induced photocatalysis, electrosynthesis, enzyme catalysis, and others. Each of these techniques aims at accessing complex molecules while limiting ecological footprint. Over the last decade, the metal-catalyzed C–H activation established itself as one of the most

• previously inaccessible molecules could be expected. C–H activation reactions, generally do not change the oxidation state of the metal and are favored in the case of aromatic or vinylic substrates but are clearly more challenging when using aliphatic precursors [21][22][23][24][25][26][27][28]. In parallel

In silico rationalisation of selectivity and reactivity in Pd-catalysed C–H activation reactions

• Liwei Cao,
• Mikhail Kabeshov,
• Steven V. Ley and
• Alexei A. Lapkin

Beilstein J. Org. Chem. 2020, 16, 1465–1475, doi:10.3762/bjoc.16.122

• intermediates of palladium-catalysed carbon–hydrogen (C–H) activation reactions as well as to predict the final products. Implemented as a high-performance computing cluster tool, it has been shown to correctly choose the mechanism and rationalise regioselectivity of chosen examples from open literature reports

• . The developed methodology is capable of predicting reactivity of various substrates by differentiation between two major mechanisms – proton abstraction and electrophilic aromatic substitution. An attempt has been made to predict new C–H activation reactions. This methodology can also be used for the

• automated reaction planning, as well as a starting point for microkinetic modelling. Keywords: C–H activation; density functional theory; reaction prediction; Introduction Periodically, our knowledge of chemistry is enriched with new transformations that provide significant breakthroughs by enabling new

Synthesis of esters of diaminotruxillic bis-amino acids by Pd-mediated photocycloaddition of analogs of the Kaede protein chromophore

• Esteban P. Urriolabeitia,
• Pablo Sánchez,
• Alexandra Pop,
• Cristian Silvestru,
• Eduardo Laga,
• Ana I. Jiménez and
• Carlos Cativiela

Beilstein J. Org. Chem. 2020, 16, 1111–1123, doi:10.3762/bjoc.16.98

• complexes 4. Treatment of 4 with CO in a MeOH/NCMe mixture promoted the methoxycarbonylation of the palladated carbon and the release of the corresponding ortho-functionalized 1,3-diaminotruxillic bis-amino esters 5 as single isomers. Keywords: amino acids; C–H activation; Kaede protein; oxazolones

• a very complex mixture was obtained and a pure compound could not be isolated. Complexes 3 were obtained as air- and moisture-stable solids in good yields (see Experimental and Supporting Information File 1). In general, the yields were higher than 85%, which shows that the C–H activation is a

• is remarkable that the C–H activation allows in this case scale-up of the reaction without a loss of yield. For oxazolone 2h the reaction was carried out using 4.3 mmol of starting material and the final yield of analytically pure 3h was 94% (see Experimental). The characterization of complexes 3