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

• 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

• simplest involves 1,8-dibromonaphthalene with a double C–H bond functionalization of benzene derivatives. This method, which employs Pd-catalyzed intermolecular and then intramolecular activation of arene C–H bonds, tolerates several useful substituents on the arene, such as fluoro, chloro, methoxy

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

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

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

• functionalizations. As the C(sp2)–C(sp3) bond is the most common building unit in organic skeletons, the Co-catalyzed formation of C(sp2)–C(sp3) bonds via C–H bond functionalization, notably via the CDC strategy, is an interesting and challenging research field that has attracted much attention in recent years. In

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

• 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

• ], amidines [11], isothioureas [12][13], whereas thioureas [14][15], ureas [16], phosphoric acids [17][18], and squaramides [19][20] fall into the second category. The Friedel–Crafts reaction, discovered by Charles Friedel and James Crafts in 1877 allows the aromatic C–H bond functionalization through the

• aromatic substitution involved isatin-derived ketimines 49 as the electron-demanding partner to achieve this aromatic p-C–H bond functionalization framing an all substituted stereocenter at the C3 position of the oxindole scaffold in the products 60. A very low reaction temperature (−55/−60 °C) was ideal

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

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

• also achieving selectivity is difficult due to its ubiquitous nature [40]. The metal-catalyzed C–H bond functionalization is a good strategy for synthesizing highly functionalized organic frameworks. In this context, the C–H alkylation is one of the most important C–C bond-formation reactions [41][42

• complex assisting in the reduced energy barrier of a rollover cyclometallation pathway and results in selective and efficient hydroarylation of the alkenes and alkynes. This was the first report for the role of a “rollover” cyclometallation pathway catalytically leading to double C–H bond

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

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

• sulfur-containing fluorinated groups. Although the transition-metal-catalyzed direct C–H bond functionalization appeared to be a powerful tool for the installation of C–C, C–N, or C–O bonds, the direct formation of a C(sp2)–SRF or a C(sp3)–SRF bond remains a challenging task. In this context, key players

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

• . 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

• functionalization using DABCO as a hydrogen atom abstractor in a photocatalytic strategy for synthetic purposes. In this context, our work aims to broaden the scope of DABCO-promoted photocatalytic C–H functionalization including formyl bonds of aldehydes as substrates (Figure 2e). The acyl radicals generated

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

•  30C). A straightforward method for an α-amino C−H bond functionalization was described by Kang et al. in 2020 to promote the synthesis of tetrahydroquinolines from tertiary anilines (Scheme 31B and C) [163]. Tetrahydroquinolines are a class of compounds already known to present varied biological

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

• −Miyaura cross-coupling produced a series of 5-aryl-4-ethynyl triazoles 136 in the presence of Pd(PPh3)4 as catalyst and K3PO4 as base in 1,4-dioxane as solvent at 100 °C (Scheme 39) [62]. A paper by Sekar et al. described the synthesis of polycyclic triazoles 142 through a domino alkyne insertion and C–H

• bond functionalization reaction sequence with triazole-bearing aryl iodide 140, catalyzed by alloy-structured Pd/Cu bimetallic nanoparticles stabilized by a binaphthyl moiety, Pd/Cu-BNP 139. The Pd/Cu-BNP nanoparticles 139 were demonstrated to be an efficient and recyclable catalyst, and triazoles

Prins cyclization-mediated stereoselective synthesis of tetrahydropyrans and dihydropyrans: an inspection of twenty years

• Asha Budakoti,
• Pradip Kumar Mondal,
• Prachi Verma and
• Jagadish Khamrai

Beilstein J. Org. Chem. 2021, 17, 932–963, doi:10.3762/bjoc.17.77

• products [1][2][3][4][5][6][7][8]. Prins and related cyclization reactions [9][10], hetero-Diels–Alder cyclization [11], cyclization onto epoxides [12], Petasis–Ferrier rearrangement [13], intramolecular oxa-Michael reactions [14], cyclization through oxidative C–H bond functionalization [15], ring-closing

An atom-economical addition of methyl azaarenes with aromatic aldehydes via benzylic C(sp³)–H bond functionalization under solvent- and catalyst-free conditions

• Divya Rohini Yennamaneni,
• Vasu Amrutham,
• Krishna Sai Gajula,
• Rammurthy Banothu,
• Murali Boosa and
• Narender Nama

Beilstein J. Org. Chem. 2020, 16, 3093–3103, doi:10.3762/bjoc.16.259

• to be developed [14]. The formation of new C–C bonds through direct C–H bond functionalization in organic chemistry is attractive [15]. Such methodologies are omnipresent and facilitate sustainable organic transformations for the synthesis of complex natural products and pharmaceuticals. In the past

• years, C−H bond functionalization catalyzed by transition metals received a strong emphasis, and other different catalytic systems have also been encouraged [16][17][18][19][20]. Huang and co-workers first realized the addition of alkylazaarenes directly to unsaturated bonds via C(sp3)–H

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

• of C–H bond functionalization reactions encompasses also direct diversification of heteroaromatic compounds. Aromatic heterocycles are key molecular motifs in natural products and biologically active compounds and thus, the development of synthetic methods allowing their site-selective C–H

Copper-catalyzed remote C–H arylation of polycyclic aromatic hydrocarbons (PAHs)

• Anping Luo,
• Min Zhang,
• Zhangyi Fu,
• Jingbo Lan,
• Di Wu and
• Jingsong You

Beilstein J. Org. Chem. 2020, 16, 530–536, doi:10.3762/bjoc.16.49

• a challenging task due to the inaccessibility of the corresponding 7-halonaphthalene substrates [12]. Recently, transition metal-catalyzed C–H bond functionalization has emerged as a powerful tool to construct various biaryl skeletons [13][14][15][16][17]. The direct C7−H arylation of 1-naphthoic

• of our ongoing research on direct C–H bond functionalization [20][27][28][29], we herein represent a copper-catalyzed remote C–H arylation of PAHs with aryliodonium salts as arylating reagents (Scheme 1). This protocol is compatible with different PAH substrates including 1-naphthamides, phenanthrene

Recent developments in photoredox-catalyzed remote ortho and para C–H bond functionalizations

• Rafia Siddiqui and
• Rashid Ali

Beilstein J. Org. Chem. 2020, 16, 248–280, doi:10.3762/bjoc.16.26

• research topic in modern synthetic organic chemistry for the constructions of challenging bonds, having the foremost scope in academia, pharmacy, and industry. Therefore, the development of green, simpler, and effective methodologies to accomplish direct C–H bond functionalization is well overdue and

• of photoredox catalysts for the functionalization of inert bonds in the domain of synthetic organic chemistry. Keywords: dual catalysis; light; ortho and para C–H bond functionalization; photoredox catalysis; Introduction Over a short period of time, direct C–H bond functionalizations by photoredox

• C–H bond functionalization, which has historically been difficult to perform, was a much-awaited and demanding method in the field of modern synthetic chemistry [1][2][3][4][5][6][7][8][9][10][11][12][13][14]. As can be seen in the literature, most of the earlier work regarding C–H bond

Regioselective Pd-catalyzed direct C1- and C2-arylations of lilolidine for the access to 5,6-dihydropyrrolo[3,2,1-ij]quinoline derivatives

• Hai-Yun Huang,
• Haoran Li,
• Thierry Roisnel,
• Jean-François Soulé and
• Henri Doucet

Beilstein J. Org. Chem. 2019, 15, 2069–2075, doi:10.3762/bjoc.15.204

• Hai-Yun Huang Haoran Li Thierry Roisnel Jean-Francois Soule Henri Doucet Univ Rennes, CNRS, ISCR-UMR 6226, F-35000 Rennes, France 10.3762/bjoc.15.204 Abstract The Pd-catalyzed C–H bond functionalization of lilolidine was investigated. The use of a palladium-diphosphine catalyst associated to

• methodology provides a straightforward access to several lilolidine derivatives from commercially available compounds via one, two or three C–H bond functionalization steps allowing to tune their biological properties. Keywords: catalysis: C–C bond formation; C–H bond activation; lilolidine; palladium

• 10 mol % of CuI as catalyst in DMF at 100 °C. The late stage C–H bond functionalization of molecules represents a powerful method for the easy screening of the biological properties of compounds containing a bioactive unit. Since the seminal work by Ohta et al. on the Pd-catalyzed C–H bond

Recent advances on the transition-metal-catalyzed synthesis of imidazopyridines: an updated coverage

• Gagandeep Kour Reen,
• Ashok Kumar and
• Pratibha Sharma

Beilstein J. Org. Chem. 2019, 15, 1612–1704, doi:10.3762/bjoc.15.165

• alcohols and asymmetric sulfide oxidation [91]. Diverse reactivity, cost efficiency and variable oxidation state [Ni(0)–Ni(IV)] associated with nickel led to remarkable developments in the field of catalytic applications [68]. Nickel catalysis involved cycloaddition, cyclization, C–H bond functionalization

Functionalization of N-arylglycine esters: electrocatalytic access to C–C bonds mediated by n-Bu₄NI

• Mi-Hai Luo,
• Yang-Ye Jiang,
• Kun Xu,
• Yong-Guo Liu,
• Bao-Guo Sun and
• Cheng-Chu Zeng

Beilstein J. Org. Chem. 2018, 14, 499–505, doi:10.3762/bjoc.14.35

• electrochemical C–H bond functionalization, leading to the formation of new C–C, C–N, C–O and C–S bonds [28][29][30][31]. Herein, we report the electrochemical α-C–H functionalization of N-arylglycine esters with C–H nucleophiles using n-Bu4NI as redox catalyst (Scheme 1). The chemistry was performed in an

Mechanochemical synthesis of small organic molecules

• Tapas Kumar Achar,
• Anima Bose and
• Prasenjit Mal

Beilstein J. Org. Chem. 2017, 13, 1907–1931, doi:10.3762/bjoc.13.186

• -workers have successfully demonstrated rhodium(III)-catalyzed C–H bond functionalization under mechanochemical conditions [182]. Advantageously, the developed method adopted mild reaction conditions, i.e., in solvent-free medium and at room temperature. It required a minimum amount of toxic metal salt of

• mechanochemical C–H bond functionalization of 2-phenylpyridine (Scheme 52). With 2.2 equiv of NXS (X = Br, I) and 5 mol % of [Cp*RhCl2]2 catalyst in a mixer mill, 74% and 84% of dibromo- and diiodo derivatives of 2-phenylpyridine, respectively, were isolated within 3 h [184]. Xu and co-workers developed a

• complex [180]. Mechanochemical Ru-catalyzed olefin metathesis reaction [181]. Rhodium(III)-catalyzed C–H bond functionalization under mechanochemical conditions [182]. Mechanochemical Csp2–H bond amidation using Ir(III) catalyst [183]. Mechanochemical Rh-catalyzed Csp2–X bond formation [184

Catalytic asymmetric synthesis of biologically important 3-hydroxyoxindoles: an update

• Bin Yu,
• Hui Xing,
• De-Quan Yu and
• Hong-Min Liu

Beilstein J. Org. Chem. 2016, 12, 1000–1039, doi:10.3762/bjoc.12.98

• Recently, iridium has emerged as a powerful catalyst for C–H bond functionalization [20][21][22][23]. In 2014, Yamamoto and co-workers reported a cationic iridium complex catalyzed asymmetric intramolecular hydroarylation of α-ketoamides, yielding 3-substituted 3-hydroxy-2-oxindoles with high

Recent advances in C(sp³)–H bond functionalization via metal–carbene insertions

• Bo Wang,
• Di Qiu,
• Yan Zhang and
• Jianbo Wang

Beilstein J. Org. Chem. 2016, 12, 796–804, doi:10.3762/bjoc.12.78

• (I) complexes. In some cases, high regioselectivity and enantioselectivity have been achieved in the C–H bond insertion of small alkanes. This review highlights the most recent accomplishments in this field. Keywords: alkane; diazo compounds; C–H bond functionalization; C–H bond insertion; metal

• has witnessed some exciting advances along this line. Thus, it would be an appropriate time to summarize the field in connection with direct C–H bond functionalization. Since catalytic metal–carbene C(sp3)–H bond insertions have been discussed in a series of excellent reviews [1][2][3][4][5][6][7][8

• , the ultimate simple alkane, thus becomes an attractive goal along this line. However, the major obstacle to achieve the methane C–H bond functionalization through metal–carbene C–H insertion is the low reactivity of the methane C–H bond as compared to most of the C–H bonds in organic compounds. This

Opportunities and challenges for direct C–H functionalization of piperazines

• Zhishi Ye,
• Kristen E. Gettys and
• Mingji Dai

Beilstein J. Org. Chem. 2016, 12, 702–715, doi:10.3762/bjoc.12.70

• -studied pyrrolidine and piperidine systems, the existence of the second ring-bound nitrogen in piperazines either causes various side reactions or inhibits or diminishes the reactivity of the C–H bond. This review summarizes the current status and challenges of direct C–H bond functionalization of

• . Transition-metal-catalyzed α-C–H functionalization Transition-metal-catalyzed direct sp3 C–H bond functionalization at the α-carbon of both cyclic and acyclic amines have been a fertile research field [45][46][47]. In the case of saturated N-heterocycles however, most of the efforts have been focused on

Copper-mediated synthesis of N-alkenyl-α,β-unsaturated nitrones and their conversion to tri- and tetrasubstituted pyridines

• Dimitra Kontokosta,
• Daniel S. Mueller,
• Dong-Liang Mo,
• Wiktoria H. Pace,
• Rachel A. Simpson and
• Laura L. Anderson

Beilstein J. Org. Chem. 2015, 11, 2097–2104, doi:10.3762/bjoc.11.226

• ][38], fragment couplings [39][40][41][42], and transition metal-catalyzed C–H bond functionalization of α,β-unsaturated imines and oximes [43][44][45][46][47][48][49][50]. We were inspired by the copper-catalyzed coupling of protected α,β-unsaturated oximes and alkenylboronic acids developed by

• corresponding tri- and tetrasubstituted pyridines 9 (Scheme 2C). This use of α,β-unsaturated oxime reagents for the synthesis of pyridines is unique from transition metal-catalyzed C–H bond functionalization processes that require a regioselective migratory insertion. This route is appealing due to the