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

• of aryl sulfides by using the catalyst and the base. A catalytic cycle is shown in Scheme 4. Firstly, electrophilic Pd(TFA)2 generated from Pd(OAc)2 and TFA, which (by C–H functionalization of arene 4) led to intermediate II. Oxidative insertion of intermediate II into the N–S bond of 1 afforded

Application of N-heterocyclic carbene–Cu(I) complexes as catalysts in organic synthesis: a review

• Nosheen Beig,
• Varsha Goyal and
• Raj K. Bansal

Beilstein J. Org. Chem. 2023, 19, 1408–1442, doi:10.3762/bjoc.19.102

• and the use of a ketone was necessary to induce C–H functionalization selectivity in preference to C=C functionalization. The products were obtained in moderate to high yields (Scheme 67). 2.6 N–H and C(sp2)–H carboxylation The application of the [(IPr)CuOH] complex as catalyst for the N–H/C(sp2)–H

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

• significantly different reactivity and chemical selectivity from noble metals (Ru, Rh, Pd). Compared with noble metals, copper catalysts are cheaper and easier to obtain, making Cu more advantageous for industrial applications of C–H functionalization reactions. The Glaser–Hay reaction may be one of the oldest

• Cu-catalyzed oxidative coupling reactions [43]. However, due to complex mechanisms, Cu-catalyzed C–H functionalization reactions developed only slowly in the last decade. Since recently the Cu-catalyzed oxidative coupling has emerged as a powerful synthetic strategy due to the development of CDC

• ]. The current synthesis method depends on the reaction of organic borane with epoxy carbonyl compounds. Using the CDC reaction can save some synthesis steps [105]. Based on DDQ-mediated oxidative C–H functionalization of benzyl ethers, the mechanism can be described as a single electron transfer (SET

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

• behavior of P450 oxygenases encouraged early work on site-selective C–H functionalization [20]. Throughout their studies, it was found that manganese could perform the same HAT and RLT steps as iron at heme active sites. Groves developed the manganese tetramesitylporphine catalyst V (Scheme 2), which was

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

• of several methods for the synthesis of functionalized pyridines or their integration into an organic molecule, new methodologies for the direct functionalization of pyridine scaffolds have been developed during the past two decades. In addition, transition-metal-catalyzed C–H functionalization and

• the mechanisms involved. Keywords: C–H functionalization; heterocycles; pyridine; rare earth metal; transition-metal-catalyzed; Introduction Pyridine, one of the most important azaheterocyclic scaffolds, is found in a diverse range of bioactive natural products, pharmaceuticals, and functional

• 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

Photocatalytic sequential C–H functionalization expediting acetoxymalonylation of imidazo heterocycles

• Deepak Singh,
• Shyamal Pramanik and
• Soumitra Maity

Beilstein J. Org. Chem. 2023, 19, 666–673, doi:10.3762/bjoc.19.48

• from academia and industry. Herein, we report a direct C-3 acetoxymalonylation of imidazo heterocycles using relay C–H functionalization enabled by organophotocatalysis starring zinc acetate in the triple role of an activator, ion scavenger as well as an acetylating reagent. The mechanistic

• products with excellent yields and regioselectivity, thus confirming excellent functional group tolerability. Keywords: C–H functionalization; imidazo heterocycles; photoredox; regioselective; relay catalysis; Introduction Among all N-fused heterocycles, imidazo[1,2-a]pyridines (IPs) are the prevalent

• aerobic oxygenation approach to imidazo heterocycles II to install the hydroxymalonate unit onto I through sequential photoredox C–H functionalization. Till date, there is no report of the direct incorporation of a quaternary hydroxyalkyl, specifically a hydroxymalonyl group at the C-3 position of IPs

C3-Alkylation of furfural derivatives by continuous flow homogeneous catalysis

• Grédy Kiala Kinkutu,
• Catherine Louis,
• Myriam Roy,
• Juliette Blanchard and
• Julie Oble

Beilstein J. Org. Chem. 2023, 19, 582–592, doi:10.3762/bjoc.19.43

• system was thus found to be compatible with the realization of this type of C‒H functionalization. This process led to a significant reduction of the reaction time compared to the batch, in particular by increasing the temperature to 200–250 °C, without significant losses of activity and selectivity

Direct C2–H alkylation of indoles driven by the photochemical activity of halogen-bonded complexes

• Martina Mamone,
• Giuseppe Gentile,
• Jacopo Dosso,
• Maurizio Prato and
• Giacomo Filippini

Beilstein J. Org. Chem. 2023, 19, 575–581, doi:10.3762/bjoc.19.42

• tool to guide the development of greener and more convenient synthetic protocols [7][8][9][10][11][12]. In this context, photochemical approaches based on electron donor–acceptor (EDA) complexes have been successfully exploited to drive the direct C–H functionalization of a large number of organic

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

• reaction to afford the naphthalene product 88a. Inspired by Zhao’s seminal report on the racemic carboamination of bicyclic alkenes [53], the Cramer laboratory studied the Co-catalyzed enantioselective carboamination of bicyclic alkenes 1 via C–H functionalization in 2021 (Scheme 17) [54]. The authors

• [2.3.1]-bicyclic alkenes 158 for the synthesis of isoquinoline (160) or isoquinolone-fused bicycles 162 (Scheme 28) [74]. Compared to their previous C–H functionalization reaction (Scheme 27) [73], no ring opening was observed. This reaction with O-acetyl ketoximes was amenable to a variety of para

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