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

• functionalization method where primary, secondary, and tertiary alkyl radicals can be readily generated through the sequential anodic oxidative fragmentation of alkyl carbazates, enabling the functionalization of N-heteroarenes [7]. This transformation is particularly valuable as the cleavage of the C–O bond to

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

• -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

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

• ]-rearrangement of ene-aldimines 149, catalysed by the BINOL-derived chiral phosphoric acid (CPA) (R)-151 (Scheme 31) [46]. DFT computational analysis suggested that the reaction proceeds via a complex cascade that involves the fragmentation of ene-aldimine 149 to form an imine methylene cation, which in turn

Improved deconvolution of natural products’ protein targets using diagnostic ions from chemical proteomics linkers

• Andreas Wiest and
• Pavel Kielkowski

Beilstein J. Org. Chem. 2024, 20, 2323–2341, doi:10.3762/bjoc.20.199

• discuss the properties and applications of different chemical proteomics linkers with special focus on their fragmentation releasing diagnostic ions and how these may improve the confidence in identified active compound–peptide conjugates. The application of advanced search options improves the

• disease [2][3]. In parallel, mass spectrometry (MS) has been crucial in many areas centered around the characterization of NPs [4]. First to annotate their often complex structures using diverse fragmentation techniques [4]. Nowadays, MS is applied for the identification of NPs’ cellular protein targets

• . Acquisition techniques benefit from possible multistage ion separation and isolation, and diverse fragmentation techniques. All of that is nowadays combined in one instrument to provide greater flexibility of the spectra acquisition setup [7][8][9][10][11][12][13][14][15][16]. Given the sheer amount of data

Factors influencing the performance of organocatalysts immobilised on solid supports: A review

• Zsuzsanna Fehér,
• Dóra Richter,
• Gyula Dargó and
• József Kupai

Beilstein J. Org. Chem. 2024, 20, 2129–2142, doi:10.3762/bjoc.20.183

• reactions in a less protic and less polar solvent. Attaching catalysts to solid supports also offers the potential for enhancing catalyst stability. Boyer and co-workers reported the use of silica nanoparticle-supported eosin Y 21 as a photocatalyst in reversible addition fragmentation chain transfer (RAFT

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

Harnessing the versatility of hydrazones through electrosynthetic oxidative transformations

• Aurélie Claraz

Beilstein J. Org. Chem. 2024, 20, 1988–2004, doi:10.3762/bjoc.20.175

• /fragmentation and extrusion of nitrogen to yield the nitrile derivative 159. The transformation proceeded neither with aldehydes nor with aromatic ketones (Scheme 32) [82]. In 2008, Okimoto et al. reported the electrochemical oxidation of ketone-derived NH-allylhydrazones 160 into the corresponding azines 161

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

• the 54% and 63% yield, respectively (Table 1, entries 3 and 4). We observed an increase in Norrish II fragmentation in these cases. The observed diastereoselectivity was poor, supporting the radical character of the ring-closing event. A similar trend was observed when studying the methanesulfonyl (Ms

• (Table 1, entry 9). The notable influence of steric and electronic parameters of the PG prompted us to investigate a range of sterically diverse alkyl substituents. Interestingly, while only fragmentation products were obtained for methyl and benzyl groups (Table 1, entries 10 and 11), the sterically

Methyltransferases from RiPP pathways: shaping the landscape of natural product chemistry

• Maria-Paula Schröder,
• Isabel P.-M. Pfeiffer and
• Silja Mordhorst

Beilstein J. Org. Chem. 2024, 20, 1652–1670, doi:10.3762/bjoc.20.147

• . Furthermore, side reaction such as racemisation, fragmentation, deletions, and double or triple methylations can lead to lower yields and hinder the coupling of further amino acids after N-methylation [44]. Ribosomal synthesis in vitro. A cell-free translation system termed “protein synthesis using

Mining raw plant transcriptomic data for new cyclopeptide alkaloids

• Draco Kriger,
• Michael A. Pasquale,
• Brigitte G. Ampolini and
• Jonathan R. Chekan

Beilstein J. Org. Chem. 2024, 20, 1548–1559, doi:10.3762/bjoc.20.138

• ], the majority of the proposed structures for these known cyclopeptide alkaloids are simply predicted by MS/MS fragmentation. Therefore, we isolated ceanothine B and completed full structural characterization using NMR, Marfey’s analysis, and MS/MS fragmentation (Supporting Information File 1, Figure S2

• of a feature as CAM603 (603.29 m/z) [7]. Fragmentation indicated a core sequence of FFFY that was observed in precursor peptides found in the transcriptome (Supporting Information File 1, Figure S3). To further support this assignment, we partially purified the compound and completed Marfey’s

• isolated from Zizyphus xylopyra [33] and matches the exact mass and fragmentation of the 589.2820 m/z feature. The 555.2953 m/z feature (CAM555) appears to be a mono-methylated version of ceanothine E. Likewise, the 574.3396 m/z (CAM574) feature is consistent with a methylated analogue of homoamericine

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

• iodide leads to the formation of 23, which further undergoes 5-endo-trig cyclization, followed by fragmentation to produce an alkyl radical and a cyclic thiocarbonate 25. These alkyl radicals then interact with B2cat2 (19) to produce a variety of structurally intricate boronic esters. The reaction occurs

• DMF with the help of photoexcited Ir(ppy)3. The suggested mechanism begins with the formation of photoexcited *[Ir(III)], which promotes SET to oxalate and generates an oxalate radical anion and [Ir(IV)]. The fragmentation of the oxalate radical anion produces an alkyl radical. The radical

• homolytic N–O bond breaking that yields phthalimide and an alkoxyl radical. This alkoxyl radical can easily extract hydrogen or undergo β-fragmentation. When P(OMe)3 is present, the alkoxyl radical combines with it to generate a phosphoranyl radical. This radical easily undergoes β-scission, resulting in

Transition-metal-catalyst-free electroreductive alkene hydroarylation with aryl halides under visible-light irradiation

• Kosuke Yamamoto,
• Kazuhisa Arita,
• Masami Kuriyama and
• Osamu Onomura

Beilstein J. Org. Chem. 2024, 20, 1327–1333, doi:10.3762/bjoc.20.116

• = −2.06 V vs SCE in MeCN [47]). In the case of the reaction with electron-deficient alkenes, e.g., methyl acrylate (E1/2 = −2.1 V vs SCE) [60], reduction of alkenes is one of the competitive processes. Subsequent fragmentation of radical anion 1•− to form aryl radical species A, which then reacts with

Activity assays of NnlA homologs suggest the natural product N-nitroglycine is degraded by diverse bacteria

• Kara A. Strickland,
• Brenda Martinez Rodriguez,
• Ashley A. Holland,
• Shelby Wagner,
• Michelle Luna-Alva,
• David E. Graham and
• Jonathan D. Caranto

Beilstein J. Org. Chem. 2024, 20, 830–840, doi:10.3762/bjoc.20.75

• voltage of 4,500 V and a fragmentation voltage of 175 V. To monitor NNG, 2-NAE, and glyoxylate, extracted ion chromatograms were obtained at m/z 119.0, 105.0, and 73.0, respectively. Ammonium concentrations were determined using a glutamate dehydrogenase assay (Sigma-Aldrich) kit using the manufacturer’s

Advancements in hydrochlorination of alkenes

• Daniel S. Müller

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

• more efficient reactions with alkene 88 (Table 6). In 2022, Oestreich reported the in situ formation of HCl by Lewis acid-induced Grob fragmentation of acid chloride 92 (Scheme 15B) [68]. The inconvenience of this method is that 92 has to be prepared in two steps, including a Birch reduction (Scheme

• ) could be prevented when switching to BCl3 (10 mol %). Interestingly, toluene (94), which is generated as a byproduct of the Grob fragmentation, must react more sluggishly with the generated cationic intermediates compared to chloride, as no alkylations of toluene were reported. In 2017, the Snyder group

• hydride shifts. Regioisomeric mixtures of products as a result of methyl shifts. Applications of the Kropp procedure on a preparative scale. Curious example of polar anti-Markovnikov hydrochlorination. Unexpected and expected hydrochlorinations with AlCl3. HCl generated by Grob fragmentation of 92

New variochelins from soil-isolated Variovorax sp. H002

• Jabal Rahmat Haedar,
• Aya Yoshimura and
• Toshiyuki Wakimoto

Beilstein J. Org. Chem. 2024, 20, 692–700, doi:10.3762/bjoc.20.63

• the planar structure of 1 is consistent with the known siderophore variochelin A, originally reported from V. boronicumulans BAM-48 by Nett et al. [5]. The NMR spectra of 2 are superimposable on those of 1. However, the MS/MS of 2 differs in the fragmentation ion corresponding to a 4-acylamino-7

• C45H79O17N11, as suggested by the HRESIMS data (m/z 1044.5603 for the [M − H]− ion), indicating the loss of two methylene groups (C2H4) from 1. In addition, the MS/MS fragmentation profile of 3 was consistent with those of 1 and 2, except for the loss of 28 mass units in the N-terminal Nγ-acyl-γ-amino acid

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

• many applications as radical precursors. Mechanistically, NHPI esters undergo a reductive decarboxylative fragmentation to provide a substrate radical capable of engaging in diverse transformations. Their reduction via single-electron transfer (SET) can occur under thermal, photochemical, or

• fragmentation of 8 affords a radical species 9 in a constructive step towards initiating the radical reaction, a principal competing step is back-electron transfer (BET) to return the closed shell starting materials (Scheme 2B). A recent study showed comparable rates for fragmentation (8 ± 5 × 105 s−1) and BET

• (3.15 to 2.06 × 105 s−1) [34] when employing catalytic IrIII excited state reductants with moderate reducing potentials (E1/2red[IrIV/*IrIII] ≈ −1.13 V vs Fc0/Fc+ in MeCN) [35]. This suggests that in the absence of a sufficiently strong driving force, BET and fragmentation compete to influence the

Substituent-controlled construction of A₄B₂-hexaphyrins and A₃B-porphyrins: a mechanistic evaluation

• Seda Cinar,
• Dilek Isik Tasgin and
• Canan Unaleroglu

Beilstein J. Org. Chem. 2023, 19, 1832–1840, doi:10.3762/bjoc.19.135

• intermediates gives azafulvene-ended secondary intermediates III, V, and VI. The observed intermediates I–VI having sulfonamide or azafulvene ends are in accordance with our previous findings [26][35][36]. In addition, the observation of azafulvene I could be attributed to the fragmentation of tripyrrane 1

GlAIcomics: a deep neural network classifier for spectroscopy-augmented mass spectrometric glycans data

• Thomas Barillot,
• Baptiste Schindler,
• Baptiste Moge,
• Elisa Fadda,
• Franck Lépine and
• Isabelle Compagnon

Beilstein J. Org. Chem. 2023, 19, 1825–1831, doi:10.3762/bjoc.19.134

• wavelength-dependent laser-induced fragmentation yield. When the frequency of the laser is resonant with a vibrational mode of the molecule, the molecule absorbs the radiation and accumulates internal energy until fragmentation [13]. In previous works we have demonstrated that the monosaccharides or

• oligosaccharides resulting from the fragmentation of a larger precursor possess a very specific IR fingerprint in the 2–4 microns spectral range, that is highly valuable to resolve all types of isomers [4]. Typical experimental IR fingerprint data are shown in Figure 1: they feature the intensities of the

Radical chemistry in polymer science: an overview and recent advances

• Zixiao Wang,
• Feichen Cui,
• Yang Sui and
• Jiajun Yan

Beilstein J. Org. Chem. 2023, 19, 1580–1603, doi:10.3762/bjoc.19.116

• [59][60]. 1.3.3 Deactivation by degenerative transfer: Reversible addition-fragmentation chain transfer (RAFT) polymerization is one of the most well-established RDRP technique. It was first proposed in 1998 by Commonwealth Scientific and Industrial Research Organization (CSIRO) researchers Chiefari

α-(Aminomethyl)acrylates as acceptors in radical–polar crossover 1,4-additions of dialkylzincs: insights into enolate formation and trapping

• Angel Palillero-Cisneros,
• Paola G. Gordillo-Guerra,
• Fernando García-Alvarez,
• Olivier Jackowski,
• Franck Ferreira,
• Fabrice Chemla,
• Joel L. Terán and
• Alejandro Perez-Luna

Beilstein J. Org. Chem. 2023, 19, 1443–1451, doi:10.3762/bjoc.19.103

• atom to zinc enables this SH2 process which represents a rare example of alkylzinc-group transfer to a tertiary α-carbonyl radical. The zinc enolate thus formed readily undergoes β-fragmentation unless it is trapped by electrophiles in situ. Enolates of substrates having free N–H bonds undergo

• without subsequent fragmentation was observed starting from α-(aminomethyl)acrylates having free N–H bonds (Table 2). The reaction of Et2Zn with acrylates 5–7 afforded the desired 1,4-addition products 11–13 in 42–55% yield. Better results were obtained starting from 8a, which delivered adduct 14a in 79

• neither in the β-fragmentation (Scheme 4) nor in the addition across the carbonyl bonds. Overall, the mechanistic investigations support the scenario depicted in Scheme 9. Oxygen (in air) triggers a free-radical chain reaction between α-(aminomethyl)acrylates and dialkylzinc reagents that entails 1,4

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

• electrogeneration favor a preassembly with Ar−X that i) upon photoexcitation accesses excited states higher than the first (D1) to bolster reactivity and/or ii) following PET assists in the Ar−X•− fragmentation step. The scope was expanded using triethylphosphite (P(OEt)3), dimethyl disulfide (MeSSMe) and bis

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

• radical addition–fragmentation on the latter and most likely to shift the regioselectivity towards 6-exo-trig by a favorable interplay of polar effects [99] failed and furnished only the 1,3-diene 10. Unfortunately, when substrate 10 was subjected to the reaction conditions shown above, only tarry

Eschenmoser coupling reactions starting from primary thioamides. When do they work and when not?

• Lukáš Marek,
• Jiří Váňa,
• Jan Svoboda and
• Jiří Hanusek

Beilstein J. Org. Chem. 2023, 19, 808–819, doi:10.3762/bjoc.19.61

• detected by ESI–MS analysis of the reaction mixture as it has a different fragmentation pattern (easily loses water – see Supporting Information File 1, Figure S1) than the starting isobaric salt 6a (loses benzonitrile and thiobenzamide). However, all attempts to isolate intermediate 7a have always failed

Direct C2–H alkylation of indoles driven by the photochemical activity of halogen-bonded complexes

• Martina Mamone,
• Giuseppe Gentile,
• Jacopo Dosso,
• Maurizio Prato and
• Giacomo Filippini

Beilstein J. Org. Chem. 2023, 19, 575–581, doi:10.3762/bjoc.19.42

• -electron-transfer (BET), a suitable leaving group (LG) needs to be included in one of the precursors. In this manner, reactive intermediates (e.g., radical species) may be generated in solution through the irreversible fragmentation of the substrates [15][21][22]. These intermediates eventually react to

Strategies to access the [5-8] bicyclic core encountered in the sesquiterpene, diterpene and sesterterpene series

• Cécile Alleman,
• Charlène Gadais,
• Laurent Legentil and
• François-Hugues Porée

Beilstein J. Org. Chem. 2023, 19, 245–281, doi:10.3762/bjoc.19.23

• Criegee- or a Grob-type fragmentation to generate cyclooctadione 163. Pleuromutilin (1) was then accessed in 4 additional steps (Scheme 32). 4.5 Reductive radical cascade cyclization: toward total synthesis of (−)-6-epi-ophiobolin N (168) and (+)-6-epi-ophiobolin A (173) Despite indisputable success of