Visible-light-driven NHC and organophotoredox dual catalysis for the synthesis of carbonyl compounds

• Vasudevan Dhayalan

Beilstein J. Org. Chem. 2025, 21, 2584–2603, doi:10.3762/bjoc.21.200

• related biological branches (Scheme 2) [52]. Studer and his group efficiently developed a method to achieve the acylation of benzylic C(sp³)–H bonds via cooperative NHC and organophotocatalyzed dual catalysis. The key step in the reaction is a radical–radical cross-coupling process leading to the

• is the reduction of acylazolium C to generate a stable benzylic radical D is formed, and this extends the lifetime of the radical, allowing for radical–radical coupling reaction to afford the desired γ-aryloxy ketones 12 in good yields. The utility of this sustainable method was further demonstrated

• amide via dual catalysis. Visible-light promoted cooperative NHC/photoredox catalyzed ring-opening of aryl cyclopropanes. NHC-catalyzed benzylic C–H acylation by dual catalysis. NHC/photoredox-catalyzed three-component coupling reaction for the preparation of γ-aryloxy ketones. NHC-catalyzed silyl

Transformation of the cyclohexane ring to the cyclopentane fragment of biologically active compounds

• Natalya Akhmetdinova,
• Ilgiz Biktagirov and
• Liliya Kh. Faizullina

Beilstein J. Org. Chem. 2025, 21, 2416–2446, doi:10.3762/bjoc.21.185

• Dotson et al. [84] for cis/trans salts 159 (Scheme 30). The authors noted that photochemical experiments carried out in benzene solutions with benzylic esters cis-159 or trans-159 gave complex product mixtures. To achieve higher conversion, a photochemical reaction was carried out in the crystalline

Rotaxanes with integrated photoswitches: design principles, functional behavior, and emerging applications

• Jullyane Emi Matsushima,
• Khushbu,
• Zuliah Abdulsalam,
• Udyogi Navodya Kulathilaka Conthagamage and
• Víctor García-López

Beilstein J. Org. Chem. 2025, 21, 2345–2366, doi:10.3762/bjoc.21.179

• form selective hydrogen bonds between the carbonyl oxygen of the fumaramide unit and the N–H groups of benzylic amide rings. Upon isomerization to the cis isomer, the hydrogen-bonding interactions are weakened, enabling the macrocycle to migrate to a second recognition station [61]. Despite their

• delivery and microscale chemical reactions, by allowing the controlled merging of droplets containing different reactants without the need for traditional reaction vessels. Furthermore, Zhu and co-workers developed a rotaxane-based fluorescence switch in which photoinduced shuttling of the benzylic amide

• reported a [2]rotaxane with controlled shuttling motion of the macrocycle, which results in a reversible control over liquid crystal helical pitch [73]. The system features a benzylic amide macrocycle that shuttles between a pyridyl-acyl hydrazone site and a glycyl-β-leucine site via trans–cis

Comparative analysis of complanadine A total syntheses

• Reem Al-Ahmad and
• Mingji Dai

Beilstein J. Org. Chem. 2025, 21, 2334–2344, doi:10.3762/bjoc.21.178

• -oxidation at one of the two benzylic positions, they started with benzylic oxidation of 34 using SeO2 to provide 37, which was further oxidized to pyridine N-oxide 38. Treatment of 38 with POCl3 in DMF delivered 2-chloropyridine 39 for the subsequent Suzuki–Miyaura cross coupling with 35 to form the C2–C3

• SeO2 gave a mono-oxidation product at the undesired benzylic position. In addition, from 33 or 35, Sarpong and co-workers prepared several other lycopodium alkaloids including 8,15-dihydrohuperzine A (40), casuarinine H (41), lycoplatyrines B (42), A (6), and F (43, existing as a mixture of

Recent advances in Norrish–Yang cyclization and dicarbonyl photoredox reactions for natural product synthesis

• Peng-Xi Luo,
• Jin-Xuan Yang,
• Shao-Min Fu and
• Bo Liu

Beilstein J. Org. Chem. 2025, 21, 2315–2333, doi:10.3762/bjoc.21.177

• analogue achieved high efficiency: the bulky bromine atom sterically biased the population toward the reactive conformer I, where the benzylic C–H bond is optimally positioned for 1,6-HAT. Therefore, (S)-113 was selected as the precursor for the key photoredox reaction (Scheme 15). To prepare this, a

Enantioselective radical chemistry: a bright future ahead

• Anna C. Renner,
• Sagar S. Thorat,
• Hariharaputhiran Subramanian and
• Mukund P. Sibi

Beilstein J. Org. Chem. 2025, 21, 2283–2296, doi:10.3762/bjoc.21.174

• and NiCl2·diglyme, was used as the catalyst to obtain the coupling products 20 in good yield and high enantioselectivity. The first nickel-catalyzed asymmetric reductive cross-coupling reaction between acid chlorides 21 and secondary benzylic chlorides 22 was reported by Reisman and co-workers (Scheme

• as reductive elimination [62]. G. Liu and Stahl disclosed an elegant methodology to functionalize benzylic C–H bonds via copper catalysis [30]. Under the catalytic conditions, alkylarenes were converted to benzylic nitriles in good yields and excellent enantioselectivities. In the proposed mechanism

• , a chiral Cu(III) complex forms from an achiral benzylic radical and a Cu(II)–CN species, and subsequent reductive elimination affords the enantioenriched benzylic nitrile product. Recently, X.-Y. Liu and co-workers reported an enantioselective aminofluoroalkylation of alkenes using a Cu(I)/chiral

Electrochemical cyclization of alkynes to construct five-membered nitrogen-heterocyclic rings

• Lifen Peng,
• Ting Wang,
• Zhiwen Yuan,
• Bin Li,
• Zilong Tang,
• Xirong Liu,
• Hui Li,
• Guofang Jiang,
• Chunling Zeng,
• Henry N. C. Wong and
• Xiao-Shui Peng

Beilstein J. Org. Chem. 2025, 21, 2173–2201, doi:10.3762/bjoc.21.166

• ][221][222][223][224][225][226][227][228][229][230][231], a proposed mechanism for this reaction was depicted. Firstly, the anodic oxidation of 32a took place to give a radical cation species A that proceeded deprotonation to give benzylic radical intermediate B. Further oxidation of B afforded a

C2 to C6 biobased carbonyl platforms for fine chemistry

• Jingjing Jiang,
• Muhammad Noman Haider Tariq,
• Florence Popowycz,
• Yanlong Gu and
• Yves Queneau

Beilstein J. Org. Chem. 2025, 21, 2103–2172, doi:10.3762/bjoc.21.165

• acid (ALA), and benzylic acid (BA). These acids were oxidized and gave formaldehyde, acetaldehyde, acetone, benzaldehyde, acetophenone, and benzophenone, respectively. By increasing pH and concentration, the rate of the reactions increased, but decreased upon increasing the amount of Cl− ions (Scheme

Bioinspired total syntheses of natural products: a personal adventure

• Zhengyi Qin,
• Yuting Yang,
• Nuran Yan,
• Xinyu Liang,
• Zhiyu Zhang,
• Yaxuan Duan,
• Huilin Li and
• Xuegong She

Beilstein J. Org. Chem. 2025, 21, 2048–2061, doi:10.3762/bjoc.21.160

• benzylic oxidation to generate a para-quinone methide (pQM) intermediate. Using fusarentin 6-methyl ether as an example, pQM intermediate 10 would be generated. The C10 alcohol should successively undergo an oxa-Michael addition reaction to close the THF ring, providing 7-O-demethylmonocerin. Similarly

• might undergo benzylic oxidations and intramolecular dehydration to access a diaryltetrahydrofuran (THF) skeleton. Then, oxidation of one aryl group through phenol oxidation would generate a putative cyclohexadienone intermediate to be further captured by the other phenol to access eupodienone through a

• powerful synthetic approach. By utilizing the concept of bioinspired total synthesis, our group has achieved the total synthesis of chabranol through a Lewis acid-promoted double cyclization, total synthesis of natural products of the monocerin-family through a benzylic oxidation and oxa-Michael addition

Enantioselective desymmetrization strategy of prochiral 1,3-diols in natural product synthesis

• Lihua Wei,
• Rui Yang,
• Zhifeng Shi and
• Zhiqiang Ma

Beilstein J. Org. Chem. 2025, 21, 1932–1963, doi:10.3762/bjoc.21.151

• -epigardneral (241) (Scheme 29b). The synthesis of 244 was achieved through a similar sequence of steps: Tollens reaction of 241, regioselective oxidation of diol 242, and acidic cyclization of aldehyde 243. Compound 244 was then converted into 245 in five additional steps. The benzylic oxidative cyclization of

• (+)-dehydrovoachalotine was prepared by a selective oxidative cyclization of a 1,3-diol moiety (Scheme 30) [74]. Treatment of the known prochiral diol 246 with DDQ first oxidized the benzylic C6 position to give intermediate 247, followed by intramolecular attack of the hydroxy group to construct the tetrahydrofuran ring

• benzylic C11 position of 268 was first oxidized to generate intermediate 269, followed by intramolecular nucleophilic attack of the hydroxy group. This stereoselective cyclization constructed the tetrahydropyran ring of pentacyclic compound 270 in 92% yield and established the stereocenter at the C7

Oxetanes: formation, reactivity and total syntheses of natural products

• Peter Gabko,
• Martin Kalník and
• Maroš Bella

Beilstein J. Org. Chem. 2025, 21, 1324–1373, doi:10.3762/bjoc.21.101

• : aliphatic > allylic > benzylic. In case of trisubstituted C=C bonds, the cyclisation proceeded with retention of configuration, however, higher reaction temperatures were required due to the increased steric hindrance. Competition experiments revealed a preference for 4-exo ring closure over 5-exo, 6-exo

• decarboxylation was induced by a photochemical oxidation using an iridium catalyst, and the resulting benzylic radicals were coupled with activated alkenes through a Giese addition which was irreversible due to the strained nature of the starting radicals. As a result, radical dimerization was minimal and the 3,3

Recent advances in amidyl radical-mediated photocatalytic direct intermolecular hydrogen atom transfer

• Hao-Sen Wang,
• Lin Li,
• Xin Chen,
• Jian-Li Wu,
• Kai Sun,
• Xiao-Lan Chen,
• Ling-Bo Qu and
• Bing Yu

Beilstein J. Org. Chem. 2025, 21, 1306–1323, doi:10.3762/bjoc.21.100

• the concurrent generation of the carbon cation 55. This cation was subsequently trapped by a nucleophile, leading to the formation of product 54. This system demonstrated a broad applicability for the general nucleophilic amination of benzylic C–H bonds. The substrate's scope and selectivity were

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

• primarily focused on substrates containing activated alkenes tethered within the molecular framework. N-Arylacrylamides were employed as model substrates, and a diverse range of functionalization reagents, including those with benzylic C–H bonds, C(sp3)–H bonds adjacent to heteroatoms, di

• activated alkenes involving benzylic C(sp3)–H bonds through a cascade cyclization process (Scheme 1) [2]. This organomediated approach can be facilitated by a catalytic amount of Lewis acid. Using DTBP as the oxidant and IrCl3 as the promoter, a range of benzylic C–H bonds in arylmethanes

Synthesis of β-ketophosphonates through aerobic copper(II)-mediated phosphorylation of enol acetates

• Alexander S. Budnikov,
• Igor B. Krylov,
• Fedor K. Monin,
• Valentina M. Merkulova,
• Alexey I. Ilovaisky,
• Liu Yan,
• Bing Yu and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2025, 21, 1192–1200, doi:10.3762/bjoc.21.96

• ][77][78][79]. The latter abstracts hydrogen atom from H-phosphonate or phosphine oxide 2, thus generating P-centered radical E and hydroperoxide complex D. Subsequently, the addition of E to the double bond of enol acetate 1 leads to the formation of benzylic radical G. The latter undergoes

• hydroperoxide transfer from copper complex D with the formation of intermediate H and, therefore, regenerating Cu(I) B. Alternatively, the latter can be formed by oxidation of benzylic radical G with the formation of carbocation I. However, given that in the absence of oxygen the β-ketophosphonate was formed

• . Alternatively, 3 can be formed by hydrolysis of benzylic cation I [71]. Conclusion In summary, we have disclosed an aerobic copper(II)-mediated phosphorylation of enol acetates with H-phosphonates leading to substituted β-ketophosphonates. The suggested method is versatile and can also be applied to phosphine

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

• CuBr promoted hydrogen atom abstraction from the amide 94 resulting in the benzylic radical species 95, followed by oxidation to give acyliminium species 96. Luque and co-workers (2020) developed a biogenic carbonate of CuO–CaCO3 to catalyze solvent- and additive-free amidation reactions in air

Recent total synthesis of natural products leveraging a strategy of enamide cyclization

• Chun-Yu Mi,
• Jia-Yuan Zhai and
• Xiao-Ming Zhang

Beilstein J. Org. Chem. 2025, 21, 999–1009, doi:10.3762/bjoc.21.81

• divergent total synthesis of several Cephalotaxus alkaloids. The α-hydroxylation of cyclopentanone, followed by amide reduction and methanol elimination in one-pot, produced (−)-cephalotaxine in 9 steps. Alternatively, Riley SeO2 oxidation of 31, benzylic bromination/hydrolyzation, facial selective ketone

• reduction, and epoxidation delivered compound 33 with the required oxidation level of the cyclopentane ring. In the final stages, Meinwald rearrangement/hemiketalization in a step-wise procedure, followed by amide reduction, completed the total synthesis of (−)-cephalotine B. Alternatively, after benzylic

A convergent synthetic approach to the tetracyclic core framework of khayanolide-type limonoids

• Zhiyang Zhang,
• Jialei Hu,
• Hanfeng Ding,
• Li Zhang and
• Peirong Rao

Beilstein J. Org. Chem. 2025, 21, 926–934, doi:10.3762/bjoc.21.75

• the benzylic alcohol, a 1,2-Grignard addition and an AcOH-interrupted Nazarov cyclization. Keywords: enantioselective synthesis; interrupted Nazarov cyclization; khayanolide-type limonoids; tetracyclic framework; Introduction Limonoids, a class of tetranortriterpenoids derived biosynthetically from

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

• electrophiles 31 (Scheme 11) [50]. This methodology is distinguished by its ability to efficiently construct configurationally well-defined stereogenic centers during C–C-bond formation through the intermediacy of benzylic copper species. Initial investigations suggested that the reaction outcome was highly

• construct non-benzylic and non-allylic CF3-substituted C(sp3) stereogenic centers. The synthetic utility of this allylation process was demonstrated through the facile functionalization of the allylic moiety in the enantioenriched product 41, providing access to optically active CF3-containing compounds

Sequential two-step, one-pot microwave-assisted Urech synthesis of 5-monosubstituted hydantoins from L-amino acids in water

• Wei-Jin Chang,
• Sook Yee Liew,
• Thomas Kurz and
• Siow-Ping Tan

Beilstein J. Org. Chem. 2025, 21, 596–600, doi:10.3762/bjoc.21.46

• attributed to the methyl group in the isobutyl side chain projected into the plane of the hydantoin ring, where the end methyl groups are conformationally positioned to hinder the reaction center. In the case where a phenyl group is directly connected to the reaction center – as opposed to a benzylic

The effect of neighbouring group participation and possible long range remote group participation in O-glycosylation

• Rituparna Das and
• Balaram Mukhopadhyay

Beilstein J. Org. Chem. 2025, 21, 369–406, doi:10.3762/bjoc.21.27

• , Scheme 18) gave product 108 with higher 1,2-cis selectivity. In protocol A, the tosylamide forms an intramolecular hydrogen bonding with the benzylic oxygen forming a quasi-bicyclic intermediate acting as a 1,2-trans directing protecting group. Thus, following subsequent formation of the oxocarbenium ion

Visible-light-promoted radical cyclisation of unactivated alkenes in benzimidazoles: synthesis of difluoromethyl- and aryldifluoromethyl-substituted polycyclic imidazoles

• Yujun Pang,
• Jinglan Yan,
• Nawaf Al-Maharik,
• Qian Zhang,
• Zeguo Fang and
• Dong Li

Beilstein J. Org. Chem. 2025, 21, 234–241, doi:10.3762/bjoc.21.15

• pharmaceuticals and agrochemicals nowadays, largely due to the unique ability of fluorinated groups to influence the physicochemical and biochemical properties of molecules [1][2][3]. Among the various fluorinated functionalities, the difluoromethyl (CF2H) group and its aryl-substituted derivative, the benzylic

Streamlined modular synthesis of saframycin substructure via copper-catalyzed three-component assembly and gold-promoted 6-endo cyclization

• Asahi Kanno,
• Ryo Tanifuji,
• Satoshi Yoshida,
• Sota Sato,
• Saori Maki-Yonekura,
• Kiyofumi Takaba,
• Jungmin Kang,
• Kensuke Tono,
• Koji Yonekura and
• Hiroki Oguri

Beilstein J. Org. Chem. 2025, 21, 226–233, doi:10.3762/bjoc.21.14

• Information File 1, Figure S2 [57], and the benzylic position on the THIQ ring [58]. Indeed, termination of the reaction just after 90 minutes instead of 20 h resulted in the isolation of the fluorescent intermediate 18 in 55% yield (Scheme S1, Supporting Information File 1). Even with the use of both

Dioxazolones as electrophilic amide sources in copper-catalyzed and -mediated transformations

• Seungmin Lee,
• Minsuk Kim,
• Hyewon Han and
• Jongwoo Son

Beilstein J. Org. Chem. 2025, 21, 200–216, doi:10.3762/bjoc.21.12

• area of medicinal chemistry [93][94][95][96][97]. In 2018, Buchwald and co-workers unveiled the enantioselective synthesis of benzylic amines through the asymmetric Markovnikov hydroamidation of alkenes utilizing diphenylsilane in copper catalysis under mild reaction conditions [98]. Dioxazolones, as

Recent advances in electrochemical copper catalysis for modern organic synthesis

• Yemin Kim and
• Won Jun Jang

Beilstein J. Org. Chem. 2025, 21, 155–178, doi:10.3762/bjoc.21.9

• ][22][23][24]. Moreover, copper-catalyzed asymmetric radical cross-coupling has advanced significantly over the past decade [25][26][27], with notable examples including Liu and Stahl’s enantioselective cyanation of benzylic C–H bonds using a Cu/chiral bisoxazoline catalyst [28], along with the Peters

• 2022, Xu and co-workers established a site- and enantioselective cyanation of benzylic C(sp³)–H bonds using an electro-photochemical strategy (Figure 7) [55]. The reaction conditions show a broad substrate tolerance, and the late-stage functionalization of complex molecules derived from natural

• pair (AQDS•−, 20•+) then generate a benzylic radical 23 and a semiquinone radical ([AQDS–H]•) through proton transfer. The benzylic radical intermediate 23 subsequently reacts with the chiral copper catalyst L3Cu(II)(CN)2 (25) to form a Cu(III) complex 26, which undergoes reductive elimination to

Reactivity of hypervalent iodine(III) reagents bearing a benzylamine with sulfenate salts

• Beatriz Dedeiras,
• Catarina S. Caldeira,
• José C. Cunha,
• Clara S. B. Gomes and
• M. Manuel B. Marques

Beilstein J. Org. Chem. 2024, 20, 3281–3289, doi:10.3762/bjoc.20.272

• slight decrease observed for 5ac, with chiral (R)-1-((1-phenylethyl)amino)-1,2-benziodoxol-3-(1H)-one (2c), can be attributed to potential steric hindrance induced by the methyl group attached to the benzylic carbon, which may hinder the nucleophile’s access to the electrophilic center of the HIR. The