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

Modern flow chemistry – prospect and advantage

• Philipp Heretsch

Beilstein J. Org. Chem. 2023, 19, 33–35, doi:10.3762/bjoc.19.3

• ], wherein photoexcited decatungstate was employed. Decatungstate is an efficient and versatile hydrogen atom transfer (HAT) catalyst with a growing number of applications. The use of decatungstate in a continuous flow setup led to shorter reaction times, increased scalability, and improved safety with

Combining the best of both worlds: radical-based divergent total synthesis

• Kyriaki Gennaiou,
• Antonios Kelesidis,
• Maria Kourgiantaki and
• Alexandros L. Zografos

Beilstein J. Org. Chem. 2023, 19, 1–26, doi:10.3762/bjoc.19.1

• generation of radicals from carbonyl reduction [18] but also manganese(III) acetate as a convenient one-electron oxidant [19]. The next twenty years, the field continued to flourish mainly by way of the decipherment of hydrogen atom transfer (HAT) mechanisms, which led to the establishment of several

• ) [30]. HAT reductions of the C9–C11 alkene followed to deliver arisugacin F (35), phenylpyropene C (36), pyripyropene E (38), and phenylpyropene F (41). The steric bulk of the manganese catalyst employed suppressed the undesired reaction with tetrasubstituted alkenes and led to the exclusive reaction

• of the desired trisubstituted alkene due to stabilization of the incipient radical at C9. Furthermore, HAT reduction served to only deliver the thermodynamic product of the trans-decalin. Similarly, the C9–C11 alkene can serve as an ideal handle to C11-hydroxylated products, such as 42, through a

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

• process was explained by the unusual feature in the reactivity of the HSPyf/(SPyf)2 pair compared to other thiols and disulfides revealed by DFT calculations. In the case of the SPyf moiety the free-energy barrier for HAT between C-centered radicals and HSPyf is higher than the barrier for an SPyf group

• transfer between the C-centered radical and (SPyf)2, whereas for Me-, CF3-, Ph-, and C6F5-derived thiols and disulfides HAT is more favorable than thiyl group transfer [123]. Quinone catalysis Quinones are well known as redox-active cofactors in biochemical processes and have found wide synthetic

• application emerged in the last years. For example, a new class of synthetically available and structurally tunable HAT mediators (N-ammonium ylides) was rationally designed for electrochemical CH-oxidation [153] (Scheme 37). By computational studies N-ammonium ylides were chosen for investigation due their

One-pot double annulations to confer diastereoselective spirooxindolepyrrolothiazoles

• Juan Lu,
• Bin Yao,
• Desheng Zhan,
• Zhuo Sun,
• Yun Ji and
• Xiaofeng Zhang

Beilstein J. Org. Chem. 2022, 18, 1607–1616, doi:10.3762/bjoc.18.171

• UMB32 and UMB136 [33][34]. Zhang developed 4-aminoquinolines for the synthesis of fluorinated analogues of acetylcholinesterase (AChE) inhibitors [35] in cascade reactions, such as one-step syntheses of quinolines. Quinolin-4-ols involving histone acetyltransferases (HAT) inhibitors [36][37], as well as

Vicinal ketoesters – key intermediates in the total synthesis of natural products

• Marc Paul Beller and
• Ulrich Koert

Beilstein J. Org. Chem. 2022, 18, 1236–1248, doi:10.3762/bjoc.18.129

• with a medium pressure mercury lamp in Pyrex® glassware triggered a 1,6-HAT leading to biradical X which combined to the racemic pyrrolizidine 68 as a 1:1 mixture of diastereomers. Three more steps gave the target compound 69 in 31% overall yield. Corynoxine Hiemstra et al. used the α-ketoester moiety

Synthesis of α-(perfluoroalkylsulfonyl)propiophenones: a new set of reagents for the light-mediated perfluoroalkylation of aromatics

• Durbis J. Castillo-Pazos,
• Juan D. Lasso and
• Chao-Jun Li

Beilstein J. Org. Chem. 2022, 18, 788–795, doi:10.3762/bjoc.18.79

• readily, and is subsequently followed by a hydrogen atom transfer (HAT) process aided by the “dummy group” radical. These reagents thus fit the paradigm of a green methodology as their implicit design and photoactivity allows them to react without the use of external metal catalysts. The intrinsic

Structural basis for endoperoxide-forming oxygenases

• Takahiro Mori and
• Ikuro Abe

Beilstein J. Org. Chem. 2022, 18, 707–721, doi:10.3762/bjoc.18.71

• analysis, the group proposed that Tyr224 is involved in the catalytic mechanism of the FtmOx1-catalyzed endoperoxide formation reaction as an intermediary of hydrogen atom transfer (HAT), similar to Tyr385 in the COX reaction. In this COX-like reaction mechanism (Scheme 5), the Fe(IV)=O species oxidizes

• tyrosyl radical, first abstracts a hydrogen atom from C21 to form a substrate radical intermediate. The following reaction with molecular oxygen and the formation of an endoperoxide bridge generate the C26 radical intermediate. Finally, HAT from Tyr68 produces verruculogen and a tyrosyl radical at Tyr68

• bridge and a C3' radical. Finally, the hydroxylation at C3' by the Fe(III)-OH species yields fumigatonoid A (path 2). At the stage of intermediate 3 in path 1, HAT from an active site residue or reductant to the C3' radical in intermediate 3 generates intermediate 4. Then, the hydroxylation at C3' forms

Sesquiterpenes from the soil-derived fungus Trichoderma citrinoviride PSU-SPSF346

• Wiriya Yaosanit,
• Vatcharin Rukachaisirikul,
• Souwalak Phongpaichit,
• Sita Preedanon and
• Jariya Sakayaroj

Beilstein J. Org. Chem. 2022, 18, 479–485, doi:10.3762/bjoc.18.50

• Wiriya Yaosanit Vatcharin Rukachaisirikul Souwalak Phongpaichit Sita Preedanon Jariya Sakayaroj Division of Physical Science and Center of Excellence for Innovation in Chemistry, Faculty of Science, Prince of Songkla University, Hat Yai, Songkhla 90110, Thailand Division of Biological Science

• , Faculty of Science, Prince of Songkla University, Hat Yai, Songkhla 90110, Thailand National Biobank of Thailand (NBT), National Science and Technology for Development Agency (NSTDA), Thailand Science Park, Klong Luang, Pathumthani 12120, Thailand School of Science, Walailak University, Thasala

DABCO-promoted photocatalytic C–H functionalization of aldehydes

• Bruno Maia da Silva Santos,
• Mariana dos Santos Dupim,
• Cauê Paula de Souza,
• Thiago Messias Cardozo and
• Fernanda Gadini Finelli

Beilstein J. Org. Chem. 2021, 17, 2959–2967, doi:10.3762/bjoc.17.205

• , Universidade Federal do Rio de Janeiro 149, Athos da Silveira Ramos Ave, Rio de Janeiro RJ, 21941-909, Brazil 10.3762/bjoc.17.205 Abstract Herein we present a direct application of DABCO, an inexpensive and broadly accessible organic base, as a hydrogen atom transfer (HAT) abstractor in a photocatalytic

• HAT step energetics and determined an optimized geometry for the transition state, showing that the hydrogen atom transfer between aldehydes and DABCO is a mildly endergonic, yet sufficiently fast step. The same calculations were performed with quinuclidine, for comparison of both catalysts and the

• differences are discussed. Keywords: C–H functionalization; DABCO; HAT; photocatalysis; Introduction The functionalization of inert C–H bonds is a goal pursued by chemists from decades, due to its ubiquity in organic molecules. This strategy also dismisses tiresome protecting groups and functional group

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

• solvent-tuned [129]. In neat CH2Cl2, the reaction produced the expected β-trichloromethyl alkyl azide; however, the reaction was chemoselective for diazidation when tert-butanol was used as co-solvent. The authors hypothesized the presence of the alcohol suppresses the polar-unmatched HAT process from

• a net iminyl-nitrooxylation reaction [140]. In 2020, Wei and co-workers studied an iminyl radical-triggered 1,5-hydrogen atom transfer (HAT) and [5 + 2] annulation processes for the synthesis of azepine derivatives 170 (Scheme 36) [141]. The reaction was tolerable of both electron-donating and

• observed generating spiro succinimidetetrahydropyridine derivatives 172. To understand the chemoselectivity of the reaction, the authors performed a DFT mechanistic study. After the iminyl radical is generated it will undergo a 1,5-HAT to form the more stable alkyl radical which will add across the alkene

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

• photoinduced copper-catalyzed α-C(sp3)–H cyclization of aliphatic alcohols with o-aminobenzamide. However, the aliphatic alcohols were limited to methanol and ethanol. In this transformation, α-C(sp3)–H of MeOH/EtOH undergoes a hydrogen atom transfer (HAT) process to synthesize quinazolinones involving ligand

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

• transfer (HAT) and nickel catalysis [54]. The catalytic system consisting of iridium photocatalyst Ir[dF(CF3)ppy]2(dtbbpy)PF6, nickel catalyst NiBr2·3H2O, ligand 4,7-dimethoxy-1,10-phenanthroline (4,7-dOMe-phen), and 3-acetoxyquinuclidine was found to be optimal to afford the desired α-amino C–C coupled

• products 7 (Scheme 3). It is worth noting that 3-acetoxyquinuclidine serves as both the HAT catalyst and the base in this reaction system. Furthermore, several cyclic and acyclic amine 6 substrates were used as C‒H nucleophile coupling partners for (hetero)aryl bromides 3. Two additional examples for the

• generation of nucleophilic α-amino radicals 2-IV via a photoredox-mediated HAT process. At the same time, the in situ generated nickel(0) species 2-V by a SET process would undergo oxidative addition into aryl bromide 3, resulting in the electrophilic nickel(II)–aryl intermediate 2-VI. The rapid coupling of

Sustainable manganese catalysis for late-stage C–H functionalization of bioactive structural motifs

• Jongwoo Son

Beilstein J. Org. Chem. 2021, 17, 1733–1751, doi:10.3762/bjoc.17.122

• is also oxidized to Mn(III)/L–N3. Azide radical addition to Mn(II)/L to form Mn(III)/L–N3 was considered as a possible route. Concurrently, the photocatalyst is irradiated by blue LED light to induce hydrogen atom transfer (HAT) at the C–H bond of substrate 12, generating alkyl radicals and enabling

• to Mn(IV) takes place on the anodic surface, resulting in the formation of a trans-diazide Mn(IV) intermediate (Figure 5). The high-valent manganese(IV) complex is susceptible to HAT from the substrate 14, generating an alkyl radical [45][46]. Subsequently, further azide radical transfer from the