Recent advances in allylation of chiral secondary alkylcopper species

• Minjae Kim,
• Gwanggyun Kim,
• Doyoon Kim,
• Jun Hee Lee and
• Seung Hwan Cho

Beilstein J. Org. Chem. 2025, 21, 639–658, doi:10.3762/bjoc.21.51

• ligand L3 and the allylic electrophile 35. In contrast, a si-face attack leads to a higher-energy transition state due to significant steric repulsion. Enantioselective hydroallylation of vinyltrifluoromethyl compounds The direct functionalization of 1-trifluoromethylalkenes 38 through copper catalysis

Photoredox-catalyzed intramolecular nucleophilic amidation of alkenes with β-lactams

• Valentina Giraldi,
• Giandomenico Magagnano,
• Daria Giacomini,
• Pier Giorgio Cozzi and
• Andrea Gualandi

Beilstein J. Org. Chem. 2024, 20, 2461–2468, doi:10.3762/bjoc.20.210

• photocatalysts (PC) that act as oxidants in the excited state [27]. The direct functionalization of amides with alkenes has been a relatively underexplored area in research, as evidenced by the limited number of examples reported in the literature. An interesting observation was made by the Nicewicz group during

• -amidyl radicals uses activated N–O amide derivatives capable of generating amidyl radicals through fragmentation [18][19]. The direct formation of amidyl radicals in the presence of a carbon alkyl chain could lead to a competitive 1,5-hydrogen atom transfer (1,5-HAT) [20][21][22], limiting the direct

• functionalization of amides with alkenes under photoredox conditions. Another viable approach for amide functionalization through photoredox catalysis involves the nucleophilic addition, in the presence of base, of an amide to a radical cation obtained by oxidation of an unfunctionalized alkene moiety (Figure 1A

Electrophotochemical metal-catalyzed synthesis of alkylnitriles from simple aliphatic carboxylic acids

• Yukang Wang,
• Yan Yao and
• Niankai Fu

Beilstein J. Org. Chem. 2024, 20, 1497–1503, doi:10.3762/bjoc.20.133

• intermediates in organic synthesis for the construction of all-carbon-substituted quaternary centers (Figure 1A). However, conventional methods for the synthesis of tertiary alkylnitriles such as direct functionalization of alkylnitriles [10] and hydrocyanation of alkenes [11][12][13][14] are typically hindered

Challenge N- versus O-six-membered annulation: FeCl₃-catalyzed synthesis of heterocyclic N,O-aminals

• Giacomo Mari,
• Lucia De Crescentini,
• Gianfranco Favi,
• Fabio Mantellini,
• Diego Olivieri and
• Stefania Santeusanio

Beilstein J. Org. Chem. 2024, 20, 1412–1420, doi:10.3762/bjoc.20.123

• to afford, by a chemospecific Lewis acid-catalyzed ring-closure protocol, valuable heterocyclic N,O-aminals (Scheme 1). Results and Discussion Since the direct functionalization of N-heterocycles offers an attractive entry to important molecular targets that might otherwise require lengthy synthetic

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

• process was catalyzed by visible light in the presence of Mo(CO)6 (1 equiv) as CO source, I2 (2 equiv), and K2CO3 (3 equiv) at 120 °C in an inert reaction environment (N2) and in DMSO as solvent (Scheme 38). Functionalization through direct C–H carbonylations The direct functionalization of indoles via C

Three-component N-alkenylation of azoles with alkynes and iodine(III) electrophile: synthesis of multisubstituted N-vinylazoles

• Jun Kikuchi,
• Roi Nakajima and
• Naohiko Yoshikai

Beilstein J. Org. Chem. 2024, 20, 891–897, doi:10.3762/bjoc.20.79

• natural products and pharmaceutical agents, including antifungal drugs [1][2][3], and hence their selective preparation has attracted considerable attention from the synthetic community. Compared to methods for the de novo construction of azole heterocycles, direct functionalization of the azole N–H bond

Recent advancements in iodide/phosphine-mediated photoredox radical reactions

• Tinglan Liu,
• Yu Zhou,
• Junhong Tang and
• Chengming Wang

Beilstein J. Org. Chem. 2023, 19, 1785–1803, doi:10.3762/bjoc.19.131

• active natural products. The direct functionalization of C–H bonds in enamides offers a convenient and versatile approach to access a wide range of functionalized enamides. In 2021, Fu and his colleagues successfully developed a novel method for the stereoselective alkylation of enamides 14 using iodine

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

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

• furfural derivatives have been developed. In particular, their direct functionalization by transition-metal-catalyzed C–H activation processes [16][17][18] has become a major area of interest where only a few methods have been reported so far. Most examples concern functionalization at C5, which is the

• steps, and thus to consider the direct functionalization of furfural via the in-situ formation of furfurylimine. Furthermore, as the [Ru3(CO)11(PPh3)] comp4 catalyst showed an activity and a solubility in batch similar to comp1, we continued the optimization with the latter, triphenylphosphine being

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

• [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

Microelectrode arrays, electrosynthesis, and the optimization of signaling on an inert, stable surface

• Kendra Drayton-White,
• Siyue Liu,
• Yu-Chia Chang,
• Sakashi Uppal and
• Kevin D. Moeller

Beilstein J. Org. Chem. 2022, 18, 1488–1498, doi:10.3762/bjoc.18.156

• of the molecules placed at those sites. In the majority of such studies, the molecules to be added to the electrodes in an array are attached directly to the array either through the use of a self-assembled monolayer or direct functionalization of a carbon electrode [12][13]. Following the synthetic

Site-selective reactions mediated by molecular containers

• Rui Wang and
• Yang Yu

Beilstein J. Org. Chem. 2022, 18, 309–324, doi:10.3762/bjoc.18.35

• powerful role of molecular containers to achieve precise transformation of complex molecules. Oxidation C–H bonds are ubiquitously distributed in nearly all of the organic compounds, which makes them predominant candidates for the modification of complex molecules. Without pre-activation, direct

• functionalization of C–H bonds brings reaction economy and effectiveness. However, owing to the rifeness of the reactivity-similar C–H bonds, it is hard to achieve discriminate control over the product site-selectivity. In nature, the site-selective oxidation of C–H bonds is facilitated by enzymes with the donor

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

• products 39 with good regioselectivities. The authors proposed a tentative visible-light-driven radical chain mechanistic profile with nickel chain-walking as a key step to rationalize the C–H arylation process [78]. Alkylation The direct functionalization of C–H bonds in alkyl groups is a fundamental but

• has improved further the C–H acylation procedures by working under mild reaction conditions. Thus, Doyle and Joe reported a mild C–H acylation protocol for the direct functionalization of α-amino C(sp3)–H bonds of N-arylamines 1 with acyl electrophiles such as anhydrides 72 and 2-pyridyl thioester 73

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

Synthesis of β-triazolylenones via metal-free desulfonylative alkylation of N-tosyl-1,2,3-triazoles

• Soumyaranjan Pati,
• Renata G. Almeida,
• Eufrânio N. da Silva Júnior and
• Irishi N. N. Namboothiri

Beilstein J. Org. Chem. 2021, 17, 762–770, doi:10.3762/bjoc.17.66

• paved the way for further modification of the protocol (Scheme 1c). Direct functionalization of triazoles is an alternative strategy to access triazoles with the desired substitution pattern. However, such approaches are complicated by a low energy barrier between the N1 and N2 tautomers in solution

• -triazoles with alkynes and Rh catalysed N1 and N2 selective alkylations [24][25]. As for metal-free approaches, besides synthesizing N-alkylated triazoles via 1,3-dipolar cycloaddition of alkyl azide with enols generated from carbonyl compounds under transition metal-free conditions [26], a direct

• functionalization of triazoles under metal-free conditions has been reported. These include the Broensted acid-catalysed N2 alkylation [27], organocatalytic N1 alkylation [28][29], N2-arylation using hypervalent iodine (Scheme 1c) [30], N2-alkylation involving radical intermediate [31], pyridine-N-oxide-mediated N1

Synthetic approaches to bowl-shaped π-conjugated sumanene and its congeners

• Shakeel Alvi and
• Rashid Ali

Beilstein J. Org. Chem. 2020, 16, 2212–2259, doi:10.3762/bjoc.16.186

• they are the most trustworthy strategies for direct functionalization of aromatic scaffolds [50]. As can be inspected from Scheme 18, monoiodosumanene 79 was obtained by gold-catalyzed iodination in the presence of N-iodosuccinimide (NIS). The mononitrosumanene 80 was achieved through the nitration

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

• directed ortho-metalation should exhibit visible-light absorption property and thus, under visible-light irradiation, the overall catalytic cycle could benefit from the photocatalytic activation. Following the initial hypothesis, the direct functionalization of phenylpyridine substrates turned out to be

• harvest visible light and triggers the expected transformation at room temperature. Undirected C–H activation In parallel to the development of the field of metal-catalyzed directed C–H activation, reactions involving the direct functionalization of simple aromatic compounds, depleted of a coordinating

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

• developing machine learning models for predicting reaction outcomes. C–H activation reactions allow conversion of relatively inexpensive and abundant hydrocarbons into the more sophisticated value-added molecules [11]. With the notion of step-economical and environmentally friendly synthesis, direct

• functionalization of C–H bonds is a powerful strategy for the synthesis and derivatization of organic molecules [12]. Homogeneous catalysis employing transition metal complexes has been widely accepted as one of the most efficient ways to perform C–H activation-based synthesis with high selectivity under relatively

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

• oxidation of alcohols and representative substrate scope. Introduction of H-bonding network in the ligand coordination sphere. Well-defined isatin copper complexes. Catalyst control in the biomimetic phenol ortho-oxidation. Structural diversity accessible by direct functionalization. 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

• ] and pharmaceuticals [10][11]. Consequently, the direct functionalization of this scaffold has attracted significant interest in recent years. Even though many transformations have been realized via a cross-dehydrogenative coupling approach [12][13] (e.g., arylations [14][15], cyanomethylation [16

Recent advances in Cu-catalyzed C(sp³)–Si and C(sp³)–B bond formation

• Balaram S. Takale,
• Ruchita R. Thakore,
• Elham Etemadi-Davan and
• Bruce H. Lipshutz

Beilstein J. Org. Chem. 2020, 16, 691–737, doi:10.3762/bjoc.16.67

Six-fold C–H borylation of hexa-peri-hexabenzocoronene

• Mai Nagase,
• Kenta Kato,
• Akiko Yagi,
• Yasutomo Segawa and
• Kenichiro Itami

Beilstein J. Org. Chem. 2020, 16, 391–397, doi:10.3762/bjoc.16.37

• , Nagoya, 464-8602, Japan 10.3762/bjoc.16.37 Abstract Hexa-peri-hexabenzocoronene (HBC) is known to be a poorly soluble polycyclic aromatic hydrocarbon for which direct functionalization methods have been very limited. Herein, the synthesis of hexaborylated HBC from unsubstituted HBC is described. Iridium

One hundred years of benzotropone chemistry

• Arif Dastan,
• Haydar Kilic and
• Nurullah Saracoglu

Beilstein J. Org. Chem. 2018, 14, 1120–1180, doi:10.3762/bjoc.14.98

Regioselective (thio)carbamoylation of 2,7-di-tert-butylpyrene at the 1-position with iso(thio)cyanates

• Anna Wrona-Piotrowicz,
• Marzena Witalewska,
• Janusz Zakrzewski and
• Anna Makal

Beilstein J. Org. Chem. 2017, 13, 1032–1038, doi:10.3762/bjoc.13.102

• ; pyrene; thioamide; Introduction Direct functionalization of pyrene 1 has attracted a great deal of attention in recent years because it is the most straightforward route to novel organic molecular materials for optoelectronic devices (OLEDs, field-effect transistors, fluorescent sensors, dye lasers, etc

Cationic Pd(II)-catalyzed C–H activation/cross-coupling reactions at room temperature: synthetic and mechanistic studies

• Takashi Nishikata,
• Alexander R. Abela,
• Shenlin Huang and
• Bruce H. Lipshutz

Beilstein J. Org. Chem. 2016, 12, 1040–1064, doi:10.3762/bjoc.12.99

• intermediate, characterized by X-ray analysis. Roles of various additives in the stepwise process have also been studied. Keywords: arylation; cationic palladium; C–H functionalization; green chemistry; olefination; Introduction Transition metal-catalyzed, direct functionalization of aryl C–H bonds has made