Biobased carbon dots as photoreductants – an investigation by using triarylsulfonium salts

• Valentina Benazzi,
• Arianna Bini,
• Ilaria Bertuol,
• Mariangela Novello,
• Federica Baldi,
• Matteo Hoch,
• Alvise Perosa and
• Stefano Protti

Beilstein J. Org. Chem. 2025, 21, 1024–1030, doi:10.3762/bjoc.21.84

• , with particular attention to the 1,2-difunctionalization of olefins by alkyl halides via atom transfer radical addition processes in the presence of amorphous nitrogen-doped carbon dots (Scheme 1a) [20]. In the framework of this research topic, we decided to investigate the use of carbon dots as

• solution was examined, for solubility reasons. a) CDs-mediated 1,2-difunctionalization of alkenes by alkyl halides R–Y and b) light-driven reduction of triarylsulfonium salts in the presence of CDs. Carbon dots tested in this project and their main (photo)physical characteristics. Emission parameters for

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

• asymmetric difunctionalization of terminal alkynes through a cascade process involving initial hydroboration followed by a hydroallylation (Scheme 15) [57]. Employing a catalytic system consisting of (R)-DTBM-Segphos (L4) and CuBr resulted in the exclusive 1,1-difunctionalization of aryl- and alkyl

• -substituted terminal alkynes 42, including the industrially relevant acetylene and propyne. Interestingly, switching to the ligand (S,S)-Ph-BPE (L1) resulted in the asymmetric 1,2-difunctionalization of aryl-substituted terminal alkynes 42. The high levels of regio- and stereoselectivity achieved under mild

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

• bromine radical attack that leads to the formation of a cationic brominated copper complex 77. Anodic oxidation and subsequent proton transfer provide the desired product 73 and regenerate the copper catalyst. Olefin addition Hydrofunctionalization and difunctionalization of alkenes are valuable methods

• for synthesizing complex molecules from alkenes, a readily available feedstock [65]. Particularly, transition-metal-catalyzed difunctionalization has recently been extensively investigated, and asymmetric reactions have been developed [66]. Many approaches rely on the addition of a radical species to

• -coupling approach to generate difunctionalization products through reductive elimination. Recently, electrocatalytic difunctionalization has been developed, and dual catalytic systems combining transition-metal catalysis with electrocatalysis have emerged [68]. In 2019, Lin et al. reported the Cu-catalyzed

Cu(OTf)₂-catalyzed multicomponent reactions

• Sara Colombo,
• Camilla Loro,
• Egle M. Beccalli,
• Gianluigi Broggini and
• Marta Papis

Beilstein J. Org. Chem. 2025, 21, 122–145, doi:10.3762/bjoc.21.7

• -difunctionalization of alkenes carried out with carbazates (N-aminocarbamates) and (hetero)arene nucleophiles or amines exploiting N-(tert-butyl)-N-fluoro-3,5-bis(trifluoromethyl)benzenesulfonamide (NFBS) as intermolecular hydrogen-atom-transfer reagent results in alkylarylation processes (Scheme 5) [19]. The

• directly to the alkene, then reacts with the nucleophile to afford product 7. The regioselective 1,2-difunctionalization of allyl alcohol has been developed as a three-component cascade reaction using arenes and sulfonamides as nucleophiles to achieve arylation/hydroamination processes. The reaction

Enantioselective regiospecific addition of propargyltrichlorosilane to aldehydes catalyzed by biisoquinoline N,N’-dioxide

• Noble Brako,
• Sreerag Moorkkannur Narayanan,
• Amber Burns,
• Layla Auter,
• Valentino Cesiliano,
• Rajeev Prabhakar and
• Norito Takenaka

Beilstein J. Org. Chem. 2024, 20, 3069–3076, doi:10.3762/bjoc.20.255

• -difunctionalization of borylenynes by catalytic conjugative cross-coupling [42]. Allenylation reagents that require regio-controlling auxiliaries such as a trimethylsilyl group (Scheme 2a) add steps before and/or after the reaction, thus they are less efficient in terms of atom- and step-economy [21][22][23][24][33

Advances in radical peroxidation with hydroperoxides

• Oleg V. Bityukov,
• Pavel Yu. Serdyuchenko,
• Andrey S. Kirillov,
• Gennady I. Nikishin,
• Vera A. Vil’ and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2024, 20, 2959–3006, doi:10.3762/bjoc.20.249

• intermediate D and on to product 95. Difunctionalization of unsaturated С–С bonds with ROO fragment With C-containing second component Alkyl fragment: The first example of the alkylation–peroxidation of C=C double bonds using TBHP and C–H as partner has been reported in 1995 on the example of Cu-catalyzed

• . Then the alkene interacts with the C-centered radical C leads to the formation of radical species D. Finally, recombination of D and B results in the formation of the target difunctionalization product 98. Related methods were subsequently proposed for the modification of coumarins 99 [92] in the

• of radical particles D and E, respectively. Further, recombination of D and E with radicals B and C results in the formation of the target difunctionalization product 101. Alkylation–peroxidation of coumarins 102 also was realized without metal catalyst (Scheme 36) [93]. Firstly, the tert-butoxy

Recent advances in transition-metal-free arylation reactions involving hypervalent iodine salts

• Ritu Mamgain,
• Kokila Sakthivel and
• Fateh V. Singh

Beilstein J. Org. Chem. 2024, 20, 2891–2920, doi:10.3762/bjoc.20.243

A review of recent advances in electrochemical and photoelectrochemical late-stage functionalization classified by anodic oxidation, cathodic reduction, and paired electrolysis

• Nian Li,
• Ruzal Sitdikov,
• Ajit Prabhakar Kale,
• Joost Steverlynck,
• Bo Li and
• Magnus Rueping

Beilstein J. Org. Chem. 2024, 20, 2500–2566, doi:10.3762/bjoc.20.214

• , which reported the merger of electrochemistry and bioconjugation in 2018 (Scheme 4b) [11]. In 2020, Zheng and coworkers developed an interesting iodoamination of indoles using unactivated amines and benzotriazoles [12]. This difunctionalization reaction was carried out in an undivided cell with an RVC

• functionalization. Difunctionalizations of double and triple bonds are of high interest as they allow the introduction of two functional groups in a single step. An interesting electrochemical difunctionalization of styrene and cyclic olefin derivatives has been reported by the Hu group [23]. They combined

• was demonstrated by the LSF of primary natural and pharmaceutical amines carrying potential competing nucleophiles, such as tryptamine and primaquine (Scheme 16). In the context of electrochemical difunctionalizations the Lei group published a transition-metal-free electrochemical difunctionalization

Hydrogen-bond activation enables aziridination of unactivated olefins with simple iminoiodinanes

• Phong Thai,
• Lauv Patel,
• Diyasha Manna and
• David C. Powers

Beilstein J. Org. Chem. 2024, 20, 2305–2312, doi:10.3762/bjoc.20.197

• ), Koser’s reagent (PhI(OH)OTs), Zhdankin’s reagent (C6H4(o-COO)IN3, ABX), and Dess–Martin periodinane (DMP) – and find application in an array of synthetically important transformations including olefin difunctionalization, carbonyl desaturation, alcohol oxidation, and C–H functionalization [3][4

From perfluoroalkyl aryl sulfoxides to ortho thioethers

• Yang Li,
• Guillaume Dagousset,
• Emmanuel Magnier and
• Bruce Pégot

Beilstein J. Org. Chem. 2024, 20, 2108–2113, doi:10.3762/bjoc.20.181

• difunctionalization led to lower yields (2e,f). The product of rearrangement 2a was oxidized into the sulfoxide and re-engaged under the optimized conditions to afford the compound of bis-rearrangement 2g in a good yield of 49%. This compound is then the result of an iterative rearrangement. Difluorinated sulfoxides

Hypervalent iodine-catalyzed amide and alkene coupling enabled by lithium salt activation

• Akanksha Chhikara,
• Fan Wu,
• Navdeep Kaur,
• Prabagar Baskaran,
• Alex M. Nguyen,
• Zhichang Yin,
• Anthony H. Pham and
• Wei Li

Beilstein J. Org. Chem. 2024, 20, 1405–1411, doi:10.3762/bjoc.20.122

• of handling, and versatile reactivity, etc. render these catalysts highly attractive for adoption in organic synthesis. In particular, the field of olefin difunctionalization, known for its rapid assembly of molecular complexity, has been a fertile ground for innovation for hypervalent iodine

• electrophilicity of the halogen source could be modulated to render different classes of nucleophiles for additions onto olefins in various olefin difunctionalization reactions [48][49][50][51][52]. In particular, we demonstrated that addition of either a Lewis acid or a base could activate amides to couple with

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

• difunctionalization of alkynes with various heteroatom and carbon nucleophiles [27][28][29][30][31][32][33][34]. Specifically, intermolecular trans-iodo(III)functionalization of alkynes has been achieved using oxygen nucleophiles such as alcohols [28][32], ethers [33], carboxylic acids [31], phosphate esters [31

• iodoazolation reaction, highlighting the unique utility of the iodine(III) electrophile in the present alkyne difunctionalization. With the standard conditions (Table 1, entry 1) in hand, we explored the scope of the three-component N-vinylation (Scheme 2). First, various azoles were subjected to the vinylation

• difunctionalization reaction to afford the product 4ag in 62% yield. While sluggish, trimethylsilylacetylene was selectively azolated at the terminal position (see 4ah), which could be rationalized by the better stabilization of a partial positive charge at this position by the β-silyl substituent. Finally, an

Palladium-catalyzed three-component radical-polar crossover carboamination of 1,3-dienes or allenes with diazo esters and amines

• Geng-Xin Liu,
• Xiao-Ting Jie,
• Ge-Jun Niu,
• Li-Sheng Yang,
• Xing-Lin Li,
• Jian Luo and
• Wen-Hao Hu

Beilstein J. Org. Chem. 2024, 20, 661–671, doi:10.3762/bjoc.20.59

• electrophilic trapping of onium ylides generated from metal carbenes with nucleophiles, providing an ingenious difunctionalization strategy for diazo compounds to access structurally complex and diverse molecules (Scheme 1b, top) [28][29]. In recent years, radical-mediated MCRs with diazo compounds have become

• a highly emerging area of research and exhibit complementary reactivity to those well-developed carbene-mediated MCRs [30][31][32][33][34][35][36][37][38][39][40][41][42]. In the radical-mediated difunctionalization of alkenes, the carbon-centered radical species from a diazo compound can add to

• diverse alkenes followed by a diradical coupling or radical addition process to achieve the difunctionalization (Scheme 1b, middle) [32][33][34][35][36][37]. However, to the best of our knowledge, the methodology involving the addition of a carbon radical from a diazo compound onto the double bond of an

Mechanisms for radical reactions initiating from N-hydroxyphthalimide esters

• Carlos R. Azpilcueta-Nicolas and
• Jean-Philip Lumb

Beilstein J. Org. Chem. 2024, 20, 346–378, doi:10.3762/bjoc.20.35

• the difunctionalization of styrenes [68] (Scheme 17B). The catalytic cycle for the styrene difunctionalization reaction is depicted in Scheme 18. First, EDA complex 88 consisting of RAE 58 and the PTH1 catalyst is formed. Under blue light irradiation, intra-complex SET leads to the formation of PTH

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

• reacted with thiosulfonates 70 and N-arylthiosuccinimides 1 as thiolating reagents. 1,2-Thiosulfonylethenes 71 were obtained via vicinal thiosulfonylation. However, in the case of 1,1-dithioethenes 69, germinal disulfenylation occurred. In addition, 1,2-difunctionalization of indole-derived 1,1

• . Co-catalyzed C2-sulfenylation and C2,C3-disulfenylation of indole derivatives. Plausible catalytic cycle for Co-catalyzed C2-sulfenylation and C2,C3-disulfenylation of indoles. C–H thioarylation of electron-rich arenes by iron(III) triflimide catalysis. Difunctionalization of alkynyl bromides with

• thiosulfonates and N-arylthio succinimides.· Suggested mechanism for difunctionalization of alkynyl bromides with thiosulfonates and N-arylthio succinimides. Synthesis of thioesters, acyl disulfides, ketones, and amides by N-thiohydroxy succinimide esters. Proposed mechanism for metal-catalyzed selective

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

• addition to alkenes and radical decarboxylation, with many of these being driven by light energy. RLT in alkene functionalization Outside of the realm of C–H activation, RLT has been leveraged to afford complex medicinal scaffolds in alkene difunctionalization. A recent example can be found in the merger

• paradigm with photocatalytic ATRA to enable the modular difunctionalization of alkenes under reagent control (Scheme 3). In Stephenson’s photocatalytic ATRA reports, the C–X bond in the product was proposed to be formed through both direct quenching of a transient alkyl radical by halogen atom transfer

• instead of the halide included in the alkyl halide reagent, limiting the ability to form different difunctionalization products. Taking inspiration from Groves’ bio-inspired manganese tetradentate manganese catalysts, we found we could instead functionalize the transient alkyl radical via RLT from a

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

• coupling partners to either propagate the reaction or to terminate the process. This review presents a comprehensive examination of domino reactions involving strained bicyclic alkenes. Rather than being exhaustive in the range of potential difunctionalization processes covered, the review will be limited

• difunctionalization of norbornene derivatives 15 with alkynes (Scheme 3) [35]. It was noted the reaction is amenable to both electron-donating groups (EDGs) and electron-withdrawing groups (EWGs); however, yields were diminished with increasing electron deficiency. Moreover, the use of the bulkier tert

• product 19c, the latter was obtained in a greatly reduced yield, perhaps due to less ring strain providing a thermodynamic driving force. In 2013, Mannathan et al. discussed a Ni-catalyzed intermolecular three-component difunctionalization of oxabicyclic alkenes 1 with organoboronic acids 20 and alkynes

Total synthesis of grayanane natural products

• Nicolas Fay,
• Rémi Blieck,
• Cyrille Kouklovsky and
• Aurélien de la Torre

Beilstein J. Org. Chem. 2022, 18, 1707–1719, doi:10.3762/bjoc.18.181

• reductively closed using SmI2. The synthesis of fragment 25 began with commercially available cyclohexenone (21), which underwent a copper-catalyzed vicinal difunctionalization with vinylmagnesium bromide and DMPU and trapping using methyl cyanoformate, leading to the formation of ketoester 22 (Scheme 4

Redox-active molecules as organocatalysts for selective oxidative transformations – an unperceived organocatalysis field

• Elena R. Lopat’eva,
• Igor B. Krylov,
• Dmitry A. Lapshin and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2022, 18, 1672–1695, doi:10.3762/bjoc.18.179

• mainly as mediators of oxidative electron transfer (SET mechanism). For example, one-electron oxidative properties of triarylamine cation radicals were used for the vinylarene difunctionalization with the formation of thiadiazolidine 1,1-dioxides that can be further transformed to the corresponding 1,2

Iron-catalyzed domino coupling reactions of π-systems

• Austin Pounder and
• William Tam

Beilstein J. Org. Chem. 2021, 17, 2848–2893, doi:10.3762/bjoc.17.196

• with the reductive addition or difunctionalization of the π-system; however, it has been demonstrated the radical intermediate can go through a SET oxidation/elimination to recover the initiating π-functionality. In this review, Fe-catalyzed domino coupling reactions involving π-systems will be

• of the alkyl radical generating the cross-coupled product cannot be ruled out [57][60]. In 2020, Gutierrez and co-workers developed a Fe-catalyzed intra- and intermolecular difunctionalization of vinyl cyclopropanes 14 with alkyl bromides 13 and aryl Grignard reagents 2 (Scheme 4) [61]. Using

• generating a benzylic radical which can be oxidized by Ag(I) to afford the corresponding benzylic cation. Nucleophilic trapping with an amine will produce the final product. In the same year, Song and co-workers reported a dehydrogenative 1,2-difunctionalization of conjugated alkenes 107 with silanes 92 and

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

• thiocyanate to generate 4-alkyl/aryl-2-aminothiazoles. Mechanistic experiments demonstrated that the photocatalyst formed in situ from Cu(OAc)2 and ammonium thiocyanate promoted the intermolecular cyclization (Scheme 7). 3.2 Difunctionalization of alkenes The 1,2-difunctionalization of alkenes is a versatile

• strategy for the construction of complex molecules. The primary process involved in the 1,2-difunctionalization of alkenes catalyzed by copper complexes is an atom-transfer radical addition (ATRA). Copper complexes or copper-based photoredox-active complexes formed in situ serve as photocatalysts to

• with oxime esters. Oxo-azidation of vinyl arenes. Azidation/difunctionalization of vinyl arenes. Photoinitiated copper-catalyzed Sonogashira reaction. Alkyne functionalization reactions. Alkynylation of dihydroquinoxalin-2-ones with terminal alkynes. Decarboxylative alkynylation of redox-active esters

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

• regenerate the nickel(0) species 21-VI and the carboxylate product 21-IX. Olefin difunctionalization Nickel-catalyzed alkene 1,2-difunctionalization is considered as useful method for preparing complex molecules in a single-step reaction [137][138][139]. In this aspect, the groups by Kong [140] and Molander

• -acylsuccinimides. Proposed catalytic cycle for the photoredox nickel-catalyzed aldehyde C–H functionalization. Proposed mechanism for the photoredox carboxylation of methylbenzenes with CO2. Proposed catalytic cycle for the decatungstate photo-HAT and nickel catalysis enabled alkene difunctionalization. Proposed

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

• yields and enantioselectivities when subjected to four sequential reactions mediated by a cooperative catalysis of a NHC organocatalyst with LiCl in the presence of DPQ as an oxidant, as shown in Scheme 17. Recently, Chen et al. used a NHC catalyst 59 in γ,δ-difunctionalization of coumarins 56 through an

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

• were found to be unreactive, probably due to steric hindrance. The one-pot difunctionalization of arenes involving a sequential C–O cleavage and C(sp2)–H activation mediated by chromium was recently reported by Luo and Zeng [124]. The reaction allows an ortho-directed diarylation of o

• reaction was kept at room temperature to avoid the difunctionalization, and the oxidant was added only in the second step. Following this route, six examples were obtained with moderate yields (56–70%, Scheme 16C). Although the use of chromium catalysis is still considered challenging due to the high

α,γ-Dioxygenated amides via tandem Brook rearrangement/radical oxygenation reactions and their application to syntheses of γ-lactams

• Mikhail K. Klychnikov,
• Radek Pohl,
• Ivana Císařová and
• Ullrich Jahn

Beilstein J. Org. Chem. 2021, 17, 688–704, doi:10.3762/bjoc.17.58

• defined combinations of chiral epoxides and chiral amides. This represents a very rare example of an oxidative geminal C–C/C–O difunctionalization next to carbonyl groups. The resulting dioxygenated allylic amides are subsequently subjected to persistent radical effect-based 5-exo-trig radical cyclization

• -allylic 2-silylacetamides would provide an intermediate alkoxide from which the Brook rearrangement and subsequent oxygenation could proceed (Scheme 1C). This represents in the event a geminal C–C/C–O difunctionalization of amide 8 and results in the α,γ-dioxygenated N-allylic amides 9. Thermal radical

• represents an oxidative C–C/C–O difunctionalization at the α-position of the amides. With correct configuration combination of chiral epoxides 7 and chiral amides 8, 2,4-dioxygenated amides 9 can be obtained with good anti-diastereoselectivity and enantioselectivity. Dioxygenated amides 9 are convenient