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

• hydrogen atom transfer (HAT)/chiral copper dual catalytic system that achieved regiodivergent and enantioselective C(sp3)–C(sp3) and C(sp3)–N oxidative cross-couplings between N-arylglycine ester/amide derivatives and abundant hydrocarbon C(sp3)–H feedstocks (Scheme 6) [24]. This methodology also

Red light excitation: illuminating photocatalysis in a new spectrum

• Lucas Fortier,
• Corentin Lefebvre and
• Norbert Hoffmann

Beilstein J. Org. Chem. 2025, 21, 296–326, doi:10.3762/bjoc.21.22

• involving π–π-stacking [75]. The resulting radical anion releases NO also yielding the anion 63. Electron transfer to the radical cation of the photocatalyst regenerates it. In this step, the neutral radical 64 is also formed. Hydrogen abstraction (hydrogen atom transfer, HAT) yields compound 65. NO and the

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

• products with high enantioselectivity. The catalytic cycle is depicted in Figure 7. The photoexcited photocatalyst anthraquinone (AQ*) acts as a hydrogen-atom transfer (HAT) acceptor and transforms the alkylarene 20 into benzylic radical intermediate 23 together with reduced [AQ–H]•. The benzylic radical

• group across alkenes 27. This reaction is applicable not only to a wide range of terminal styrenes but also to internal alkenylarenes, enynes, and allenes, providing enantioenriched products in good yields with high enantioselectivities. This reaction involves Co-catalyzed HAT and Cu-catalyzed

• enantioselective radical cyanation. In the proposed catalytic cycle, Co(III)–H species 92 are initially formed from the anodically oxidized Co(III) complex 91 and hydrosilane 88 (Figure 15). Subsequently, the HAT between the Co(III)–H catalyst 92 and the alkene 27 generates a carbon-centered radical species 93

Giese-type alkylation of dehydroalanine derivatives via silane-mediated alkyl bromide activation

• Perry van der Heide,
• Michele Retini,
• Fabiola Fanini,
• Giovanni Piersanti,
• Francesco Secci,
• Daniele Mazzarella,
• Timothy Noël and
• Alberto Luridiana

Beilstein J. Org. Chem. 2024, 20, 3274–3280, doi:10.3762/bjoc.20.271

• pathway for the functionalization of an electron-deficient olefin is the Giese reaction (Figure 1) [6][7]. This reaction involves the hydroalkylation of the olefin via radical addition (RA), followed by either hydrogen-atom transfer (HAT) or single-electron transfer (SET) and protonation. Traditionally

• photocatalytic activation (Figure 1b) [17][18][19][20][21]. A photocatalytic HAT or SET generates the corresponding boryl, α-amino or silyl radical, which can abstract a halogen atom from alkyl halides to form the corresponding alkyl radical. However, the use of TTMS as a XAT reagent had already been established

• slight increase in chemical yield. Giese reaction: Radical addition on olefins with an electron-withdrawing group (EWG) followed by a HAT or SET and protonation; halogen-atom transfer: (a) tin-mediated XAT, (b) XAT initiated by a photocatalyst (PC) and mediated by boranes (B), silanes (Si) or alkylamines

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

• functional groups can be functionalized for any synthetic need via HAT or β-scission with subsequent C-centered radical formation [10][11][12][13]. Also, peroxy radicals play a key role in the chemistry of the Earth's lower atmosphere [14][15][16]. The traditional approaches to organic peroxide synthesis

• tendency to recombine with C-centered radicals and add to unsaturated bonds with the formation of new carbon–oxygen bonds. However, alkoxy radicals, which are always present in such systems, are involved not only in the formation of ROO radicals but also in hydrogen atom transfer (HAT) processes and β

• generate the nucleophilic carbon radical B. The intramolecular 1,5-HAT of B provided the alkyl radical C, which then cross-coupled with the in situ-generated high-valent Mnn+1OO-t-Bu species to form the 1,6-difunctionalized product 42 via peroxy-ligand transfer. The remote trifluoromethylthiolation

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

• method for the hydrolysis of hydrosilanes to silanols using N-hydroxyphthalimide (NHPI) as the hydrogen-atom-transfer (HAT) mediator [38]. To demonstrate the potential of their approach, they showcased the LSF of natural products such as (−)-borneol and (+)-fenchol, as well as pharmaceutical drugs

• including ibuprofen, febuxostat, and gemfibrozil, achieving moderate to good yields. The proposed mechanism involves the oxidation and deprotonation of NHPI at the cathode to form phthalimide-N-oxyl (PINO) radicals. These PINO radicals act as HAT reagents, abstracting a hydrogen atom from the Si–H bond of

• authors, the reaction proceeds via hydrogen-atom transfer (HAT) at the benzylic position, mediated by DDQ (2,3-dichloro-5,6-dicyano-1,4-benzoquinone). The proposed mechanism includes two possible pathways: In path A, the benzylic position undergoes HAT to form a benzyl radical, which is then oxidized by

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

• the linked alkene moiety, followed by hydrogen transfer from the hydrogen atom transfer (HAT) catalyst. This process was used to successfully prepare 2-alkylated clavam derivatives. Keywords: β-lactam; acridinium photocatalyst; alkenes; amides; intramolecular radical reaction; photoredox catalysis

• -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

• ) [23][24][25]. The nucleophilic attack of the nitrogen atom on the oxidized C=C double bond results in the formation of a radical intermediate after deprotonation. This radical intermediate can proceed through various pathways (e.g., HAT, oxidation) to yield the desired final product. In the

Asymmetric organocatalytic synthesis of chiral homoallylic amines

• Nikolay S. Kondratyev and
• Andrei V. Malkov

Beilstein J. Org. Chem. 2024, 20, 2349–2377, doi:10.3762/bjoc.20.201

• deracemisation of an unsaturated amine 144 was reported by Li Dang and Xin-Yuan Liu (Scheme 30) [45]. They used CF3-radical-induced remote CH-activation, combined with Brønsted acid-catalysed chiral hydrogen atom transfer (HAT). In this reaction, triphenylphosphine first mediated the addition of the CF3-radical

Efficacy of radical reactions of isocyanides with heteroatom radicals in organic synthesis

• Akiya Ogawa and
• Yuki Yamamoto

Beilstein J. Org. Chem. 2024, 20, 2114–2128, doi:10.3762/bjoc.20.182

• reaction into B–H or B–B bonds has been reported, but the reactions by a radical mechanism are largely unknown. Very recently, Turlik and Schuppe reported a novel generation of nucleophilic boryl radicals using hydrogen atom transfer (HAT) and photoredox catalysis. Furthermore, its reaction with

Multicomponent syntheses of pyrazoles via (3 + 2)-cyclocondensation and (3 + 2)-cycloaddition key steps

• Ignaz Betcke,
• Alissa C. Götzinger,
• Maryna M. Kornet and
• Thomas J. J. Müller

Beilstein J. Org. Chem. 2024, 20, 2024–2077, doi:10.3762/bjoc.20.178

• hydrolactite catalysts (C-Mg-Al HAT-3) [90]. With β-ketoesters, the method can be extended to a four-component synthesis. Initially, β-ketoesters react with hydrazine to form pyrazolones, while a Knoevenagel reaction between malononitrile and aldehyde simultaneously generates a Michael system. Both

Ring opening of photogenerated azetidinols as a strategy for the synthesis of aminodioxolanes

• Henning Maag,
• Daniel J. Lemcke and
• Johannes M. Wahl

Beilstein J. Org. Chem. 2024, 20, 1671–1676, doi:10.3762/bjoc.20.148

• synthesis of azetidinols. Mechanistically, the Norrish–Yang cyclization involves a 1,5-hydrogen abstraction (HAT) step followed by ring closure to forge the azetidine scaffold (Scheme 2a, 1 → 3, via 1,4-biradical 2) [26]. The respective α-aminoacetophenones 1 were synthesized using a modular approach

Benzylic C(sp³)–H fluorination

• Alexander P. Atkins,
• Alice C. Dean and
• Alastair J. J. Lennox

Beilstein J. Org. Chem. 2024, 20, 1527–1547, doi:10.3762/bjoc.20.137

• benzylic fluorination method that employed unprotected amino acids as radical precursors, Figure 12 [50]. Oxidation of glycine by Ag(II) promotes decarboxylation and results in the α-amino radical, which performs a HAT on the benzylic substrate to furnish the benzylic radical. This subsequently undergoes

• mechanism. Excess NFSI functioned as both a fluorine source and HAT reagent precursor (Figure 13) [20]. Fluorine abstraction from NFSI by copper(I) generates an N-centred radical that is selective for benzylic C(sp3)–H bonds [52][53], affording the benzylic radical via HAT. Subsequent FAT with the in situ

• detailed metal-free radical C(sp3)–H fluorinations suitable for benzylic substrates. These typically involve the generation of a HAT reagent that is selective for benzylic C–H bonds and facilitates the generation of a benzylic radical. Subsequent FAT, from a fluorinating reagent, yields the desired benzyl

Generation of alkyl and acyl radicals by visible-light photoredox catalysis: direct activation of C–O bonds in organic transformations

• Mithu Roy,
• Bitan Sardar,
• Itu Mallick and
• Dipankar Srimani

Beilstein J. Org. Chem. 2024, 20, 1348–1375, doi:10.3762/bjoc.20.119

• phosphoranyl radical intermediate then undergoes β-cleavage, giving rise to a benzylic radical and triphenylphosphine oxide. A terminal hydrogen atom transfer (HAT), facilitated by an aryl thiol, results in the formation of the desired product with concurrent formation of the thiyl radical. The reduction of

•  21). Styrenes selectively reacted with vinyl ethers in the presence of an acridinium photocatalyst and a diphenyl disulfide HAT catalyst to produce the aldehyde product when exposed to blue LED light. Differently substituted styrenes were examined using this protocol, which produced the aldehyde

• breakdown of ethyl vinyl ether and trapping of ethanol, yielding radical 84. To regenerate the photocatalyst, PhSSPh functioned as an oxidant. After protonation upon the β-elimination step, PhS− contributed a hydrogen atom to both 83 and 84, alongside regeneration of the HAT catalyst. Lastly, the acetal

Advancements in hydrochlorination of alkenes

• Daniel S. Müller

Beilstein J. Org. Chem. 2024, 20, 787–814, doi:10.3762/bjoc.20.72

• transfer (MH HAT) reactions (Figure 6A). As pointed out by Shenvi in a recent review [11], the major difference between traditional polar hydrochlorinations of alkenes and MH HAT is that the latter is far more chemoselective and proceeds under “milder” conditions. As shown in Figure 7B, carbocations or

• carbenium ions are highly energetic species which tend to react unselectively according to the reactivity–selectivity principle. In contrast, MH HAT produces relatively stable radicals which is demonstrated by, e.g., the strong difference of heat of formation of the tert-butyl radical and cation (Figure 7B

• ) [78]. Another advantage of the MH HAT process is that the α-C–H bond in the corresponding radical is comparatively stable, whereas a carbocation has superacidic α-C–H bonds with a pKa of ≈ −17 [79]. Therefore, polar hydrochlorination reactions are in competition with elimination reactions which is not

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

• hydrogen atom transfer (HAT) or sequential electron transfer and proton transfer (ET/PT) steps. Alternatively, redox-neutral transformations can be envisioned using catalytic reductants, which can enable a complementary scope of downstream functionalizations (Scheme 2B). In this perspective, we present an

• CO2. Radical 12 undergoes intermolecular addition to the olefin acceptor 13 to form radical intermediate 14. Finally, under reductive conditions radical 14 can undergo hydrogen atom transfer (HAT) or sequential electron transfer and proton transfer (ET/PT) to form the conjugate addition product 15

• ester (complex 68). This process delivers substrate radical 9 and nicotinyl radical 69 following proton transfer to the phthalimidyl anion. Then, addition of 9 to α,β-unsaturated ester 70 yields radical intermediate 71. At this stage, HAT mediated by another equivalent of BuNAH delivers product 72, with

Additive-controlled chemoselective inter-/intramolecular hydroamination via electrochemical PCET process

• Kazuhiro Okamoto,
• Naoki Shida and
• Mahito Atobe

Beilstein J. Org. Chem. 2024, 20, 264–271, doi:10.3762/bjoc.20.27

• electron-transfer to give the corresponding radical species through oxidative X–H bond cleavage. One such species is the amidyl radical, which is broadly synthetically useful as a nitrogen source in hydroamination reactions and as a hydrogen atom transfer (HAT) reagent for remote C–H activation [2][3][4][5

• avoided [9]. The initial aim of this study was the electrochemical generation of an amidyl radical as a HAT source for the synthesis of 1’-C functionalized nucleosides via the generation of an anomeric radical species from uridine derivative 1 (Figure 1, bottom) [10]. Although the HAT reaction failed

• exclusively obtained, implying that the expected HAT at the 1’-C position to afford 2 (Table 1, entry 1) had not occurred. In contrast, the reaction efficiency was significantly decreased in the absence of the phosphate base (Table 1, entry 2), and electricity is necessary to proceed the reaction (Table 1

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

• radical and I· played a pivotal as an intermediate step in the production of alkyl iodides B. Compound B could undergo a further elimination reaction to yield various olefins 11. Regarding benzyl substrates, the radical I· demonstrated its efficacy as a reagent for hydrogen atom transfer (HAT

A deep-red fluorophore based on naphthothiadiazole as emitter with hybridized local and charge transfer and ambipolar transporting properties for electroluminescent devices

• Suangsiri Arunlimsawat,
• Patteera Funchien,
• Pongsakorn Chasing,
• Atthapon Saenubol,
• Taweesak Sudyoadsuk and
• Vinich Promarak

Beilstein J. Org. Chem. 2023, 19, 1664–1676, doi:10.3762/bjoc.19.122

• electroluminescent (EL) performance of TPECNz, non-doped OLED employing TPECNz as an emissive layer (EML) was fabricated through thermal evaporation of the optimized device configuration of ITO/1,4,5,8,9,11-hexaazatriphenylene-hexacarbonitrile (HAT-CN) (6 nm)/N,N'-bis(naphthalen-1-yl)-N,N'-bis(phenyl)benzidine (NPB

• ) (30 nm)/tris(4-carbazoyl-9-ylphenyl)amine (TCTA) (10 nm)/TPECNZ (60 nm)/1,3,5-tris(1-phenyl-1H-benzimidazol-2-yl)benzene (TPBi) (40 nm)/LiF (1 nm)/Al (100 nm), in which ITO and Al served as anode and cathode, respectively (Figure 7a). Herein, HAT-CN and LiF were used as the hole- and electron

Visible-light-induced nickel-catalyzed α-hydroxytrifluoroethylation of alkyl carboxylic acids: Access to trifluoromethyl alkyl acyloins

• Feng Chen,
• Xiu-Hua Xu,
• Zeng-Hao Chen,
• Yue Chen and
• Feng-Ling Qing

Beilstein J. Org. Chem. 2023, 19, 1372–1378, doi:10.3762/bjoc.19.98

• light-induced charge transfer event to give trifluoroethoxyl radical B, followed by a 1,2-hydrogen atom transfer (HAT), producing the stable radical C. For the nickel cycle, it is initiated by oxidative addition of Ni(0) catalyst E to acyl electrophile D formed in situ from carboxylic acid 1 with

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

• ) from the DHP substrates to DDQ, a hydrogen atom transfer (HAT), and counter anion exchange of In(OTf)3 might happen to generate ion pair A. In(OTf)3 coordinates with the carbonyl oxygen atoms in dimethyl malonate 188 to provide activated complex B for subsequent addition to A furnishing product 189

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

• , such as hydrogen atom transfer (HAT), alkene addition, and decarboxylation. At least as important has been innovation in radical functionalization methods, including radical–polar crossover (RPC), enabling these intermediates to be engaged in productive and efficient bond-forming steps. However, direct

• driven by several key features of RLT catalysis, including the ability to form diverse bonds (including C–X, C–N, and C–S), the use of simple earth abundant element catalysts, and the intrinsic compatibility of this approach with varied radical generation methods, including HAT, radical addition, and

• functionalization of alkyl radicals, with successful synthetic reactions requiring efficiency and selectivity in both of these processes and inherent compatibility between each. Radical generation has benefitted from many general mechanistic approaches, including hydrogen atom transfer (HAT) [5], alkene addition [6

Photoredox catalysis harvesting multiple photon or electrochemical energies

• Mattia Lepori,
• Simon Schmid and
• Joshua P. Barham

Beilstein J. Org. Chem. 2023, 19, 1055–1145, doi:10.3762/bjoc.19.81

• neutral PDI and forms the aryl halide’s radical anion, which then undergoes C(sp2)–X bond fission to afford the aryl radical as a reactive intermediate. The aryl radical then either reacts via hydrogen atom transfer (HAT) with solvent molecules or Et3N•+ in an overall dehalogenation to furnish product 2

• halides and the coupling products were obtained in good yields (52–74%) (Figure 4B). To suppress the rapid HAT with solvent DMF that yields the dehalogenated product, DMSO was chosen as solvent for the C–H arylation. When applying the catalytic protocol to 2-allyloxy-1,3,5-tribromobenzene, the 5-exo-trig

• ., through protonation and successive reduction or HAT) that upon excitation also acts as a super-reductant (Figure 8C). Simultaneously, Jacobi von Wangelin, Pérez-Ruiz and co-workers introduced the structurally related 9,10-dicyanoanthracene (DCA) as a conPET catalyst. Excitation of PET-generated radical

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

• deliver the desired product 11 and the undesired product 12), or an hydrogen-atom-transfer (HAT) process (which would not place a formal negative charge onto the molecule), where the hydrogen atom required for this possible final HAT step originates from the solvent (DMF) itself [107]. Therefore, we

Sulfate radical anion-induced benzylic oxidation of N-(arylsulfonyl)benzylamines to N-arylsulfonylimines

• Joydev K. Laha,
• Pankaj Gupta and
• Amitava Hazra

Beilstein J. Org. Chem. 2023, 19, 771–777, doi:10.3762/bjoc.19.57

• -aryl(benzyl)amines to N-arylimines using K2S2O8 is reported to be problematic, the oxidation of N-(arylsulfonyl)benzylamines to N-arylsulfonylimines using K2S2O8 has been achieved for the first time. The dual role of the sulfate radical anion (SO4·−), including hydrogen atom abstraction (HAT) and

• abstraction (HAT) followed by single electron transfer (SET) enabled by the sulfate radical anion (SO4·−). Results and Discussion Initially, we investigated the reaction of N-benzenesulfonyl(benzyl)amine (1a) as a model substrate with K2S2O8 in MeCN at 80 °C for 12 h, conditions that were used earlier in our

• abstracts the activated NH proton to produce imine 2. The dual role of SO4·− involving HAT and SET is proposed in this plausible mechanism, which requires further investigation. Similarly, a plausible mechanism for the one-pot synthesis of N-heterocycles is shown in Scheme 6. Initially, the N

Combretastatins D series and analogues: from isolation, synthetic challenges and biological activities

• Jorge de Lima Neto and
• Paulo Henrique Menezes

Beilstein J. Org. Chem. 2023, 19, 399–427, doi:10.3762/bjoc.19.31

• trypanosomiasis (HAT) has not yet been performed. Structures of some members of the combretastatin D series, corniculatolides, and isocorniculatolides. ED50 values of the combretastatin D family against murine P388 lymphocytic leukemia cell line (approximated values of molar concentration after conversion) [55