Recent advances in oxidative radical difunctionalization of N-arylacrylamides enabled by carbon radical reagents

• Jiangfei Chen,
• Yi-Lin Qu,
• Ming Yuan,
• Xiang-Mei Wu,
• Heng-Pei Jiang,
• Ying Fu and
• Shengrong Guo

Beilstein J. Org. Chem. 2025, 21, 1207–1271, doi:10.3762/bjoc.21.98

Recent advances in synthetic approaches for bioactive cinnamic acid derivatives

• Betty A. Kustiana,
• Galuh Widiyarti and
• Teni Ernawati

Beilstein J. Org. Chem. 2025, 21, 1031–1086, doi:10.3762/bjoc.21.85

Recent advances in controllable/divergent synthesis

• Jilei Cao,
• Leiyang Bai and
• Xuefeng Jiang

Beilstein J. Org. Chem. 2025, 21, 890–914, doi:10.3762/bjoc.21.73

• undergoes intramolecular cyclization into a proximal C(sp2)–H bond (ΔG‡ = +19.7 kcal·mol−1) to form Int-46, which reacts with 4-MePhSH (ΔG‡ = +14.9 kcal·mol−1) to yield radical intermediate Int-47 and a thiyl radical (4-MePhS·). Sequential thiol-assisted hydrogen shifts produce Int-48, followed by

Deep-blue emitting 9,10-bis(perfluorobenzyl)anthracene

• Long K. San,
• Sebastian Balser,
• Brian J. Reeves,
• Tyler T. Clikeman,
• Yu-Sheng Chen,
• Steven H. Strauss and
• Olga V. Boltalina

Beilstein J. Org. Chem. 2025, 21, 515–525, doi:10.3762/bjoc.21.39

• higher selectivity with milder reaction temperatures. The weaker C(sp2)–Br bond is easier to cleave than a C(sp2)–H bond, resulting in a higher likelihood of radical substitution at those positions. To the best of our knowledge, there are no previous examples of perfluorobenzyl substitution of any PAH(Br

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

• copper is mainly to activate the C(sp2)–H bond by coordination or activating the oxidant to achieve the reaction cycle. Subsequently, Li and Ahmad et al. reported a Cu(I)-catalyzed C(sp2)–H activation and ether formation of C(sp2)–C(sp3) bonds via CDC, respectively (Scheme 14) [65][66]. The isotope

• the substrate achieved the activation of the C(sp2)–H bond. Other non-noble metal-catalyzed reactions In 2013, Liu et al. reported that MnO2 could catalyze the CDC of the benzylic C(sp3)–H bond in benzyl ethers with α-carbonyl C(sp3)–H bonds in the presence of air at room temperature (Scheme 33) [98

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

• metal-catalyzed directed and undirected, proximal as well as distal pyridine C(sp2)–H bond functionalizations in detail under different types of reactions. Further, this review excludes the use of pyridine as a directing group for C–H functionalizations and the C–H functionalization of fused pyridines

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

• polysubstituted derivative 21g was also functionalized in high yield (71%). Pleasingly, other metals have been also successfully applied for the trifluoromethylthiolation of aromatic derivatives by C(sp2)–H bond activation such as Rh(III) and Co(III)-based catalysts as depicted below. Rhodium catalysis: In 2015

• were obtained in 30% and 20% yields, respectively. Several mechanistic experiments revealed that the C(sp2)–H bond activation step was reversible and represented the rate-determining step (KIE = 2.4). First, the chelation of the palladium(II) catalyst with the bidentate directing group, followed by the

• C(sp2)–H bond activation involving a concerted metalation–deprotonation pathway affords the metallacycle K. After an oxidative addition in the N-SCF3 bond of the Munavalli reagent V, the palladium(IV) species L is obtained. Finally, the reductive elimination affords the product and regenerates the

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

• has been selectively feasible without activating a C(sp2)–H bond in the arene moiety. Verma and co-workers [91] have reported the use of VO(acac)2 immobilized over graphitic carbon nitride (VO@gC3N4) under visible light irradiation to perform a photocatalytic C–H activation of arene methides and

Recent advances in transition-metal-catalyzed incorporation of fluorine-containing groups

• Xiaowei Li,
• Xiaolin Shi,
• Xiangqian Li and
• Dayong Shi

Beilstein J. Org. Chem. 2019, 15, 2213–2270, doi:10.3762/bjoc.15.218

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

Intramolecular cascade annulation triggered by rhodium(III)-catalyzed sequential C(sp²)–H activation and C(sp³)–H amination

• Liangliang Song,
• Guilong Tian,
• Johan Van der Eycken and
• Erik V. Van der Eycken

Beilstein J. Org. Chem. 2019, 15, 571–576, doi:10.3762/bjoc.15.52

• activation; rhodium; acrylamide; heterocycles; Introduction Over the last decade, transition metal-catalyzed C(sp2)–H activation has emerged as an efficient strategy to access complex molecules [1][2][3][4][5][6]. Among the methodologies, RhIII-catalyzed oxidative annulation of a C(sp2)–H bond with 2π

Transition metal-free oxidative and deoxygenative C–H/C–Li cross-couplings of 2H-imidazole 1-oxides with carboranyl lithium as an efficient synthetic approach to azaheterocyclic carboranes

• Lidia A. Smyshliaeva,
• Mikhail V. Varaksin,
• Pavel A. Slepukhin,
• Oleg N. Chupakhin and
• Valery N. Charushin

Beilstein J. Org. Chem. 2018, 14, 2618–2626, doi:10.3762/bjoc.14.240

• nucleophilic reagents. This feature enables one to carry out the direct nucleophilic functionalization of the C(sp2)–H bond, thus leading to novel C(5)-modified 2H-imidazoles. We have established that carboranyllithium, generated in situ from 1,2-dicarba-closo-dodecaborane [66], can be involved in the above

Cobalt- and rhodium-catalyzed carboxylation using carbon dioxide as the C1 source

• Tetsuaki Fujihara and
• Yasushi Tsuji

Beilstein J. Org. Chem. 2018, 14, 2435–2460, doi:10.3762/bjoc.14.221

• ]. Direct C(sp2)–H bond carboxylation As described above, C–H carboxylations with CO2, particularly C(sp2)–H carboxylation reactions, have attracted much research interest. As a consequence, Nolan [57] and Hou [58] independently reported Cu-catalyzed carboxylations using heteroarenes as substrates, which

• reaction mechanism for this Rh-catalyzed chelation-assisted C(sp2)–H bond carboxylation is shown in Scheme 29. First, a low-valent methyl–Rh(I) species A is generated by transmetalation. Secondly, a pyridine ring in the substrate coordinates to the Rh center, which prompts the cleavage of the adjacent C–H

• of 2-phenylpyridine 29a. Rh-catalyzed chelation-assisted C(sp2)–H bond carboxylation with CO2. Reaction mechanism for the Rh-catalyzed C(sp2)–H carboxylation of 2-pyridylarenes 29. Carboxylation of C(sp2)–H bond with CO2. Carboxylation of C(sp2)–H bond with CO2. Reaction mechanism for the Rh

Transition-metal-free synthesis of 3-sulfenylated chromones via KIO₃-catalyzed radical C(sp²)–H sulfenylation

• Yanhui Guo,
• Shanshan Zhong,
• Li Wei and
• Jie-Ping Wan

Beilstein J. Org. Chem. 2017, 13, 2017–2022, doi:10.3762/bjoc.13.199

• chromones via domino chromone ring construction and C(sp2)–H bond sulfenylation have been achieved under transition-metal-free conditions by using KIO3 as the only catalyst. Keywords: C–H sulfenylation; chromones; domino reaction; free-radical; transition-metal-free; Introduction The C–S bond-forming

• efforts in exploring enaminone C(sp2)–H bond sulfenylation [40][41] reactions have led us to establish the synthesis of 3-sulfenylated chromones via KIO3-catalyzed tandem reactions of o-hydroxylphenylenaminone and thiophenols via tandem C–H sulfenylation and intramolecular C–N bond oxygenation (B, Scheme

• developed a flexible and facile method for the synthesis of 3-sulfenylated chromones via a transition-metal-free reaction involving a C(sp2)–H bond sulfenylation. Besides the notable feature of transition-metal-free operation, the present method also displays advantages in using odourless sulfur sources

Enantioselective carbenoid insertion into C(sp³)–H bonds

• J. V. Santiago and
• A. H. L. Machado

Beilstein J. Org. Chem. 2016, 12, 882–902, doi:10.3762/bjoc.12.87

• aryldiazoacetate 21e afforded the insertion product in only 15% yield. In 2013, Davies, Yo et al reported a new strategy to construct 2,3-dihydrobenzofurans based on a sequential enantioselective rhodium catalyzed carbenoid insertion into a C(sp3)–H bond followed by a palladium C(sp2)–H bond activation to build a

Recent advances in copper-catalyzed C–H bond amidation

• Jie-Ping Wan and
• Yanfeng Jing

Beilstein J. Org. Chem. 2015, 11, 2209–2222, doi:10.3762/bjoc.11.240

• sulfonamidation and imidation) reactions under the categories of C(sp3)–H bond amidation, C(sp2)–H bond amidation, C(sp)–H bond amidation and cascade reactions initiated by C–H amidation. Review C(sp3)–H bond amidation Intermolecular amidation The formation of N-alkylamides could be traditionally accessed via

• synthesis of a lactam via chelating-group-assisted copper catalysis. As outlined in Scheme 8, the N-quinolin-8-yl substituted amides 27 could be smoothly transformed into lactams 28 and/or 28' via C–H amidation by using Cu(OAc)2 as catalyst and Ag2CO3 as a base. In a specific case, the C(sp2)–H bond could

• preferably transformed over secondary C–H bonds (Scheme 9). C(sp2)–H bond amidation The direct transformation of C(sp2)–H bonds constitutes an issue of extensive current interest. On the basis of the pioneering work in transition-metal-catalyzed activation of the C(Ar)–H bonds of electron deficient

C–H bond halogenation catalyzed or mediated by copper: an overview

• Wenyan Hao and
• Yunyun Liu

Beilstein J. Org. Chem. 2015, 11, 2132–2144, doi:10.3762/bjoc.11.230

• via direct C–H bond transformation is reviewed. Keywords: C(sp2)–H bond; C(sp3)–H bond; copper; halogenation; Introduction Organohalides are inarguably a class of most useful chemicals owing to their prevalent application in the synthesis of organic products. The versatile reactivity of C–X bonds

• catalysis in modern organic synthesis, herein, we would like to highlight the recent progress in the C–H bond halogenation with copper catalysis or mediation. Review Copper-catalyzed/mediated halogenation of the C(sp2)–H bond Halogenation of the arene C(sp2)–H bond In the synthesis of aryl halides employing

• ]. Halogenation of the alkene C(sp2)–H bond Beside the arene C–H bond, the alkene C–H is another typical C(sp2)–H bond. However, unlike the arene C–H bond, the alkene C–H bond tends to undertake difunctionalization via the cleavage of the π-bond in the presence of halogen source. Therefore, the halogenation of

Efficient synthesis of π-conjugated molecules incorporating fluorinated phenylene units through palladium-catalyzed iterative C(sp²)–H bond arylations

• Fatiha Abdelmalek,
• Fazia Derridj,
• Safia Djebbar,
• Jean-François Soulé and
• Henri Doucet

Beilstein J. Org. Chem. 2015, 11, 2012–2020, doi:10.3762/bjoc.11.218

Synthesis of phenanthridines via palladium-catalyzed picolinamide-directed sequential C–H functionalization

• Ryan Pearson,
• Shuyu Zhang,
• Gang He,
• Nicola Edwards and
• Gong Chen

Beilstein J. Org. Chem. 2013, 9, 891–899, doi:10.3762/bjoc.9.102

• excellent directing group for a range of Pd-catalyzed C–H functionalization reactions [26][27][28][29][30][31][32][33][34][35]. In 2005, the Daugulis laboratory first reported that the ortho-C(sp2)−H bond of benzylpicolinamides could be arylated with aryl iodides under Ag-promoted Pd-catalyzed conditions