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

• ][57]. Stereoselective 5,6-dihydro-1,4-dithiin-based synthesis of cis-olefins [42][58]. Addition to aldehydes and applications in stereoselective synthesis. Direct C–H functionalization methods for 1,4-dithianes [82][83]. Known cycloaddition reactivity modes of allyl cations [84][85][86][87][88][89][90

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

• easily available, which have been established as versatile synthetic building blocks for the synthesis of cyclic scaffolds [25]. In 2016, Zhu et al. reported the first example of a Rh-catalyzed C–H functionalization of enaminones with alkynes and α-diazo-β-ketoesters to access naphthalenes [26]. Very

A one-pot electrochemical synthesis of 2-aminothiazoles from active methylene ketones and thioureas mediated by NH₄I

• Shang-Feng Yang,
• Pei Li,
• Zi-Lin Fang,
• Sen Liang,
• Hong-Yu Tian,
• Bao-Guo Sun,
• Kun Xu and
• Cheng-Chu Zeng

Beilstein J. Org. Chem. 2022, 18, 1249–1255, doi:10.3762/bjoc.18.130

• the in situ generation of α-iodocarbonyl ketones from constant current electrolysis (CCE) of ketones in the presence of iodide ions. It is worth noting that we have also reported an electrochemical method for the synthesis of 2-aminothiazoles via the one-pot direct α-C–H functionalization of ketones

• demonstrate the feasibility of our idea, ethyl acetoacetate (1a) and thiourea (2a) were chosen as model substrates for the optimization of reaction conditions. Based on our previous studies on the halide-mediated α-C–H functionalization of carbonyl compounds [32][33][34][35], graphite was chosen as the

Synthesis of odorants in flow and their applications in perfumery

• Merlin Kleoff,
• Paul Kiler and
• Philipp Heretsch

Beilstein J. Org. Chem. 2022, 18, 754–768, doi:10.3762/bjoc.18.76

• review, we give an overview of selected methods for the synthesis of odorants in flow, including heterogeneously catalyzed reactions, gas reactions, and photochemical C–H functionalization processes. After a brief introduction on types of odorants, the presented odorant syntheses are ordered according to

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

• laboratories calls for a critical analysis of these methods to enable an efficient transition of these methods. Hence, manganese-catalyzed C–H functionalization for late-stage functionalizations of biomolecules and drug-like scaffolds are summarized [8]. Likewise, 3d transition metal-catalyzed C–H

• functionalization enabled the de novo assembly of bioactive molecules [9]. The full potential of the mild nature of C–H functionalization is unlocked by the merger with modern photochemistry and electrocatalysis manifolds. In this context, recent advances were realized by the combination of photoredox catalysis and

• nickel-catalyzed C–H functionalization [10]. Iron complexes are typically cost-effective and nontoxic, and therefore, their use in domino processes represents an outstanding prospect for sustainable organic syntheses [11]. Directed C–H activations have been developed as increasingly amenable tools for

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

• differences are discussed. Keywords: C–H functionalization; DABCO; HAT; photocatalysis; Introduction The functionalization of inert C–H bonds is a goal pursued by chemists from decades, due to its ubiquity in organic molecules. This strategy also dismisses tiresome protecting groups and functional group

• accessibility, it is still underused, and has only recently started to gain attention from the synthetic community. Murphy and co-workers reported the use of the DABCO radical cation, generated by a stoichiometric oxidant (TPTA-PF6), as a hydrogen abstractor for alpha-nitrogen C–H functionalization [21] (Figure

• . Alemán and co-workers also published the use of a photogenerated DABCO radical cation in a distal β-carbonyl enantioselective C–H functionalization for the synthesis of pyrroline derivatives [26] (Figure 2d). The latter is, to the best of our knowledge, the only work reporting a direct substrate C–H bond

Selective sulfonylation and isonitrilation of para-quinone methides employing TosMIC as a source of sulfonyl group or isonitrile group

• Chuanhua Qu,
• Run Huang,
• Yong Li,
• Tong Liu,
• Yuan Chen and
• Guiting Song

Beilstein J. Org. Chem. 2021, 17, 2822–2831, doi:10.3762/bjoc.17.193

• sulfones is a valuable and appealing task in synthetic chemistry. Traditionally, diarylmethyl sulfones are synthesized by transition-metal-catalyzed deoxy C–S bond-coupling reaction of sodium arylsulfinates with diarylmethanols [11], C–H functionalization of alkyl sulfones with aryl halides [12], and via a

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

• phosphoric acid-catalyzed synthesis of axially chiral compounds and to suggest that much more attention should be paid to these catalysts in order to promote asymmetric synthesis. Review 1. Enantioselective synthesis of atropisomeric biaryls Direct C–H functionalization strategies for the atroposelective

Visible-light-mediated copper photocatalysis for organic syntheses

• Yajing Zhang,
• Qian Wang,
• Zongsheng Yan,
• Donglai Ma and
• Yuguang Zheng

Beilstein J. Org. Chem. 2021, 17, 2520–2542, doi:10.3762/bjoc.17.169

• complexes to photocatalysis are reported. Copper-photocatalyzed reactions, including alkene and alkyne functionalization, organic halide functionalization, and alkyl C–H functionalization that have been reported over the past 5 years, are included. Keywords: copper-photocatalyzed reactions; green chemistry

• functionalization, organic halides functionalization, and alkyl C–H functionalization, are highlighted. Review 1. Special features of photoredox-catalyzed processes by copper complexes To understand photoredox-catalyzed processes, a discussion of the general mechanism of [Ru(bpy)3]2+ is needed [25][26][27]. When

• bonds and can be applied to radical chemistry. This review discusses copper-catalyzed reactions including alkene and alkyne, organic halide, and alkyl C–H functionalization. 3. Visible-light-mediated copper-catalyzed alkene and alkyne functionalization 3.1 Olefinic C–H functionalization and allylic

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

• ][10][11][12]. However, the above protocols generally proceeded under harsh conditions that led to poor functional group tolerance and generated stoichiometric amounts of waste. Thus far, the transition-metal-catalyzed C–H functionalization strategy has innovated the way to producing ferrocene

• 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

• Lusina Mantry Rajaram Maayuri Vikash Kumar Parthasarathy Gandeepan Department of Chemistry, Indian Institute of Technology Tirupati, Tirupati – Renigunta Road, Settipalli Post, Tirupati, Andhra Pradesh 517506, India 10.3762/bjoc.17.143 Abstract Catalytic C‒H functionalization has become a

• metallaphotoredox catalysis enabled C‒H functionalizations with unique reaction pathways under mild reaction conditions. Given the relative earth-abundance and cost-effective nature, nickel catalysts for photoredox C‒H functionalization have received significant attention. In this review, we highlight the

• 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

Catalyzed and uncatalyzed procedures for the syntheses of isomeric covalent multi-indolyl hetero non-metallides: an account

• Ranadeep Talukdar

Beilstein J. Org. Chem. 2021, 17, 2102–2122, doi:10.3762/bjoc.17.137

• ]. The reason behind the C-2 attachment of the boron atom rather than at the C-3 position of the indole ring was explained by McGough et al. [37]. They performed a base-free catalytic I2-assisted indole C–H functionalization (electrophilic borylation) using the N-protected indole 1 and NHC·borane 4a that

Asymmetric organocatalyzed synthesis of coumarin derivatives

• Natália M. Moreira,
• Lorena S. R. Martelli and
• Arlene G. Corrêa

Beilstein J. Org. Chem. 2021, 17, 1952–1980, doi:10.3762/bjoc.17.128

• % ee) (Scheme 10). A catalytic asymmetric β-C−H functionalization of ketones 33 with 4-hydroxycoumarins 1 was developed by Zhu et al. [43]. The enamine, formed via reaction of the aminocatalyst 35 with the ketone, is oxidased by IBX resulting in the electrophilic imine, which in turn undergoes a

• -hydroxycoumarin 1 with α,β-unsaturated ketones 2 catalyzed by a chiral primary amino amide 32. Catalytic asymmetric β-C–H functionalization of ketones via enamine oxidation. Enantioselective synthesis of polycyclic coumarin derivatives 37 catalyzed by an primary amine-imine catalyst 38. Allylic alkylation

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

• high importance in the field of Alzheimer’s disease studies [169]. In 2020, Xu and co-workers described an unprecedented dual C–H functionalization of indolin-2-ones and benzofuran-2-ones via an oxidative C(sp3)–H cross-coupling protocol catalyzed by inexpensive FeCl3 and ligand-free conditions (Scheme

• most studied metal applied in C–H functionalization methodologies. Cobalt-catalyzed C–H activation Cobalt is a cheap metal that presents powerful colors in its ionic forms and therefore, it has been used as a basic element in ink since ancient periods [171][172]. Cobalt alloys are used in blades [173

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

• Jongwoo Son Department of Chemistry, Dong-A University, Busan 49315, South Korea Department of Chemical Engineering (BK21 FOUR Graduate Program), Dong-A University, Busan 49315, South Korea 10.3762/bjoc.17.122 Abstract The late-stage C–H functionalization of bioactive structural motifs is a

• organic synthesis. Among the 3d metals, manganese catalysts have gained increasing attention for late-stage diversification due to the sustainability, cost-effectiveness, ease of operation, and reduced toxicity. Herein, we summarize recent manganese-catalyzed late-stage C–H functionalization reactions of

• azobenzenes was unveiled [1], manganese catalysts have exhibited a significant capacity for powerful C–H functionalization, and they have therefore been actively utilized in the area of sustainable organic syntheses [2][3][4][5][6]. Catalytic late-stage C–H functionalization, a highly efficient synthetic

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

• insensitivity to air are advantages of this reaction (Scheme 37) [60]. In 2017, De Borggraeve et al. explained a convenient procedure for the preparation of triazolo[1,5-a]indolones 131 through an intramolecular cyclization via an unprecedented Pd-catalyzed carbonylative C–H functionalization of 1-(2-bromoaryl

Heterogeneous photocatalytic cyanomethylarylation of alkenes with acetonitrile: synthesis of diverse nitrogenous heterocyclic compounds

• Guanglong Pan,
• Qian Yang,
• Wentao Wang,
• Yurong Tang and
• Yunfei Cai

Beilstein J. Org. Chem. 2021, 17, 1171–1180, doi:10.3762/bjoc.17.89

• cyanomethylarylation of N-aryl/benzoyl acrylamide or allylamine involving the key C–H functionalization of readily available acetonitrile is a straightforward and powerful method to access these useful structures [13][14][15][16][17]. Over the last decade, although numerous protocols have been disclosed for the direct

Synthetic reactions driven by electron-donor–acceptor (EDA) complexes

• Zhonglie Yang,
• Yutong Liu,
• Kun Cao,
• Xiaobin Zhang,
• Hezhong Jiang and
• Jiahong Li

Beilstein J. Org. Chem. 2021, 17, 771–799, doi:10.3762/bjoc.17.67

• electrons from the electron-rich tertiary amine nitrogen atom to the electron-deficient benzene ring, achieving intramolecular electron transfer. Selective C–H-functionalization also includes no catalysts, oxidants, additives, acids and bases, which is of great significance in the synthesis and application

Synthesis of N-perfluoroalkyl-3,4-disubstituted pyrroles by rhodium-catalyzed transannulation of N-fluoroalkyl-1,2,3-triazoles with terminal alkynes

• Olga Bakhanovich,
• Viktor Khutorianskyi,
• Vladimir Motornov and
• Petr Beier

Beilstein J. Org. Chem. 2021, 17, 504–510, doi:10.3762/bjoc.17.44

• electrophilic metal-bound iminocarbenes form. These iminocarbenes undergo a variety of intriguing reactions, such as a cycloaddition and a C–H functionalization, among others, leading mostly to nitrogen heterocycles [8][9][10]. Using this chemistry, a variety of pyrroles have been prepared starting from N

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

• -transfer-type reactions under mild conditions and in the absence of toxic radical precursors [44][45][46]. Considering, on one hand, the fundamentally appealing properties of both, metal-catalyzed C–H functionalization reactions and visible-light-induced photocatalysis, and, on the other hand, their

• of the independently formed intermediate furnished the expected coupling products under generally mild reaction conditions. Furthermore, a merge of metal-catalyzed C–H functionalization and photocatalysis was also astutely employed to design modern versions of Sonogashira-type reactions as well as

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

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

• cations and radical anions) Recently, the exploitation of alkenyl and aryl radical ions has emerged as a platform for the functionalization of small molecules. They appear as attractive intermediates for a direct alkene difunctionalization or arene C–H functionalization. In particular, radical cations are

• direct activation of the ß-C–H bond [109]. However, organic dyes have not yet been broadly applied for such transformations. Charged aryl radical species Arene radical cations are valuable intermediates that enable the direct C–H functionalization of the aromatic species. They can be accessed through the

• -Acr+ scaffold. In 2015, they developed a site-selective C–H amination of arenes (Scheme 25) [110]. The arenes 25.1 could be aminated by various N-heterocycles 25.2 for the synthesis of the C–H functionalization products 25.3 with fine-tuned Mes-di(t-Bu)Acr+ (OD4) as a photocatalyst. In this

Diversity-oriented synthesis of 17-spirosteroids

• Benjamin Laroche,
• Thomas Bouvarel,
• Martin Louis-Sylvestre and
• Bastien Nay

Beilstein J. Org. Chem. 2020, 16, 880–887, doi:10.3762/bjoc.16.79

• accessible biologically relevant materials. This second strategy can take benefit of existing functional groups on the substrate, or rely on direct C–H functionalization [20][21][22][23][24][25][26][27][28][29][30][31][32][33]. Taking steroids as an example of highly targeted privileged structures, numerous

Copper catalysis with redox-active ligands

• Agnideep Das,
• Yufeng Ren,
• Cheriehan Hessin and
• Marine Desage-El Murr

Beilstein J. Org. Chem. 2020, 16, 858–870, doi:10.3762/bjoc.16.77

• ], and perform C–H functionalization through aerobic dearomatization of phenols [35]. These broad synthetic outcomes further led to a unified approach for the preparation of 1,2-oxy-aminoarenes by phenol–amine couplings (Scheme 10) [36]. We reported the formation of a C–N bond through copper-catalyzed

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

• alkyl and allyl groups were also successfully introduced via the same method. Additionally, the typically applied N-phenyl group in the THIQ substrate could be replaced by the cleavable p-methoxyphenyl (PMP) group and successful N-deprotection was demonstrated. Keywords: C–H functionalization; C(sp3)–C

• (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

• steps for the installation and removal of the directing group. However, there is also a good number of substrates containing C–H bonds that are inherently more reactive than others in the same molecule, and in such cases a selective C–H functionalization can be achieved in the absence of any directing