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

Substitution reactions in the acenaphthene analog of quino[7,8-h]quinoline and an unusual synthesis of the corresponding acenaphthylenes by tele-elimination

• Ekaterina V. Kolupaeva,
• Narek A. Dzhangiryan,
• Alexander F. Pozharskii,
• Oleg P. Demidov and
• Valery A. Ozeryanskii

Beilstein J. Org. Chem. 2024, 20, 243–253, doi:10.3762/bjoc.20.24

• ratio. It should be recalled here that tele-elimination refers to the cleavage of molecular fragments located further than in the vicinal positions (at least three to five carbons between the hydrogen and bromine atoms in the case of 15 to give 16). This rare transformation usually results in the

Photochromic derivatives of indigo: historical overview of development, challenges and applications

• Gökhan Kaplan,
• Zeynel Seferoğlu and
• Daria V. Berdnikova

Beilstein J. Org. Chem. 2024, 20, 228–242, doi:10.3762/bjoc.20.23

• the Z-isomer with metal cations. Schematic representation of indigo-type (left) and amide-type (right) resonances in N,N'-acetylindigo (9a). Suggested intermediates for the double bond cleavage for the thermal relaxation of N,N'-diacylindigos: (A) a biradical transient species, (B) a dipolar transient

Optimizations of lipid II synthesis: an essential glycolipid precursor in bacterial cell wall synthesis and a validated antibiotic target

• Milandip Karak,
• Cian R. Cloonan,
• Brad R. Baker,
• Rachel V. K. Cochrane and
• Stephen A. Cochrane

Beilstein J. Org. Chem. 2024, 20, 220–227, doi:10.3762/bjoc.20.22

• -anomers of compound 5. It is noteworthy to mention that the benzyl ether in compound 4 exhibited successful cleavage upon treatment with sodium bromate/sodium dithionite in ethyl acetate/water, while other protecting functionalities like acetyl and phenylsulfonylethyl ester groups remained intact [45

Tandem Hock and Friedel–Crafts reactions allowing an expedient synthesis of a cyclolignan-type scaffold

• Viktoria A. Ikonnikova,
• Cristina Cheibas,
• Oscar Gayraud,
• Alexandra E. Bosnidou,
• Nicolas Casaretto,
• Gilles Frison and
• Bastien Nay

Beilstein J. Org. Chem. 2024, 20, 162–169, doi:10.3762/bjoc.20.15

• Polytechnique, CNRS, Institut Polytechnique de Paris, F-91128 Palaiseau, France Sorbonne Université, CNRS, Laboratoire de Chimie Théorique, 75005 Paris, France 10.3762/bjoc.20.15 Abstract The Hock cleavage, which is compatible with tandem processes, was applied to the synthesis of 1-aryltetralines through a

• one-pot transformation from readily available benzyl(prenyl)malonate substrates. After the photooxygenation of the prenyl moiety, the resulting hydroperoxide was directly engaged in a Hock cleavage by adding a Lewis acid. The presence of an aromatic nucleophile in the reaction mixture and that of a

• –Crafts reactions, rather than an oxocarbenium. Keywords: 1-aryltetralines; Friedel–Crafts reaction; Hock rearrangement; oxidative cleavage; tandem reactions; Introduction The Hock cleavage [1] consists in the acid-catalyzed rearrangement of organic hydroperoxides, leading to the oxidative cleavage of a

Perspectives on push–pull chromophores derived from click-type [2 + 2] cycloaddition–retroelectrocyclization reactions of electron-rich alkynes and electron-deficient alkenes

• Michio Yamada

Beilstein J. Org. Chem. 2024, 20, 125–154, doi:10.3762/bjoc.20.13

• and alkenes. The pioneering work by Bruce et al. in 1981 revealed that the cleavage of tetracyanoethylene (TCNE) under mild conditions via its reaction with metal acetylides yields metal complexes featuring the tetracyanobuta-1,3-diene (TCBD) structural motif [3]. Subsequently, numerous researchers

Photoinduced in situ generation of DNA-targeting ligands: DNA-binding and DNA-photodamaging properties of benzo[c]quinolizinium ions

• Julika Schlosser,
• Olga Fedorova,
• Yuri Fedorov and
• Heiko Ihmels

Beilstein J. Org. Chem. 2024, 20, 101–117, doi:10.3762/bjoc.20.11

• species (ROS), such peroxyl, alkoxy and hydroxyl radicals, or carbon-centered radicals, which subsequently induce DNA strand cleavage. In the type-II mechanism, a triplet-excited photosensitizer reacts with molecular oxygen to give highly reactive singlet oxygen, 1O2, as reactive intermediate, which in

• (Table 2). To assess the optimal parameters for the photoreaction, the ligand was irradiated in the presence of the DNA under anaerobic conditions at different irradiation times and concentrations of the ligand. The DNA-strand cleavage was analyzed by agarose-gel electrophoresis. In this assay, the DNA

• -strand cleavage in the supercoiled plasmid DNA pBR322 is indicated by the formation of the relaxed, open-circular form [76]. It has to be noted that under these conditions the DNA is already damaged in the absence of the photosensitizer. Therefore, each series of experiments is complemented for

Synthesis of N-acyl carbazoles, phenoxazines and acridines from cyclic diaryliodonium salts

• Nils Clamor,
• Mattis Damrath,
• Thomas J. Kuczmera,
• Daniel Duvinage and
• Boris J. Nachtsheim

Beilstein J. Org. Chem. 2024, 20, 12–16, doi:10.3762/bjoc.20.2

• mol % raised yields to synthetically useful 74% (Table 1, entry 7). The excess amount of 1a was still necessary as a significant amount of iodobiphenyl is formed under the reaction conditions as a result of an undesired heterolytic iodine–carbon bond cleavage. Other carbonate bases and changing the Cu

Long oligodeoxynucleotides: chemical synthesis, isolation via catching-by-polymerization, verification via sequencing, and gene expression demonstration

• Yipeng Yin,
• Reed Arneson,
• Alexander Apostle,
• Adikari M. D. N. Eriyagama,
• Komal Chillar,
• Emma Burke,
• Martina Jahfetson,
• Yinan Yuan and
• Shiyue Fang

Beilstein J. Org. Chem. 2023, 19, 1957–1965, doi:10.3762/bjoc.19.146

• methacrylamide group. Detritylation was not carried out in the last synthetic cycle, which would otherwise remove the polymerizable tag. A portion of the CPG was subsequently subjected to deprotection and cleavage. To prevent the potential Michael addition side reaction of acrylonitrile to nucleobases, the 2

• typical deprotection and cleavage conditions using concentrated ammonium hydroxide at elevated temperature. At this stage, the mixture contained the desired full-length sequence 3 and impurities such as failure sequences 4 and small molecules from ODN deprotection (Scheme 1). It is noted that the full

• correct sequence. In the present case, we did the 399 and 400 nt ODN syntheses at the scale of 0.1 µmol. One tenth of the CPG was subjected to deprotection and cleavage (theoretically 10 nmol). One fourth was subjected to CBP (theoretically 2.5 nmol). Quantification of 1/160 (theoretically 15.625 pmol

Beyond n-dopants for organic semiconductors: use of bibenzo[d]imidazoles in UV-promoted dehalogenation reactions of organic halides

• Kan Tang,
• Megan R. Brown,
• Chad Risko,
• Melissa K. Gish,
• Garry Rumbles,
• Phuc H. Pham,
• Oana R. Luca,
• Stephen Barlow and
• Seth R. Marder

Beilstein J. Org. Chem. 2023, 19, 1912–1922, doi:10.3762/bjoc.19.142

• strong reductants with effective potentials of ca. −2 V vs ferrocenium/ferrocene, yet are relatively stable to air due to the coupling of redox and bond-breaking processes. Here, we examine their use in accomplishing electron transfer-induced bond-cleavage reactions, specifically dehalogenations. The

• potentials of the halides that can be reduced in this way, quantum-chemical calculations, and steady-state and transient absorption spectroscopy suggest that UV irradiation accelerates the reactions via cleavage of the dimers to the corresponding radical monomers. Keywords: dehalogenation; n-dopant

• . −2 V vs FeCp2+/0, yet the dimers are reasonably stable to air due to the kinetic barriers associated with the coupling of electron-transfer and bond-cleavage reactions [26]. Here we demonstrate that (N-DMBI)2 and (Cyc-DMBI)2 (Figure 1c) can be used to accomplish dehalogenation of benzyl, alkyl, and

N-Boc-α-diazo glutarimide as efficient reagent for assembling N-heterocycle-glutarimide diads via Rh(II)-catalyzed N–H insertion reaction

• Grigory Kantin,
• Pavel Golubev,
• Alexander Sapegin,
• Alexander Bunev and
• Dmitry Dar’in

Beilstein J. Org. Chem. 2023, 19, 1841–1848, doi:10.3762/bjoc.19.136

• including the degradation of lymphoid transcription factors [15][16][17] IKZF1, IKZF3, and SALL4 where the latter's degradation could result in a significant teratogenic effect [18]. In addition, these glutarimide derivatives are highly susceptible to hydrolysis and enzymatic cleavage under physiological

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

• -dihydronaphthalenes 47 with yields of up to 92%, as depicted in Scheme 21 [38]. The key aspect of the approach involved the simultaneous cleavage of dual C–C bonds and a single N–O bond, which was facilitated by the utilization of LiI/PPh3 as the photoredox system. Amination Anilines play important roles in both

Unprecedented synthesis of a 14-membered hexaazamacrocycle

• Anastasia A. Fesenko and
• Anatoly D. Shutalev

Beilstein J. Org. Chem. 2023, 19, 1728–1740, doi:10.3762/bjoc.19.126

• the most electrophilic C2 carbon of the pyrimidine ring in 8 to give intermediate A. Cleavage of the C2–N3 bond in the latter followed by proton transfer in the formed zwitterion B affords bis-amidrazone C. Next, two molecules of bis-amidrazone C react with each other forming adduct D, which either

• ). Under these conditions, the cleavage of either the C2–N3 bond or the N1–C2 bond can proceed. In the latter case, the formed 3-amino-N-(hydrazonomethyl)-1-methyl-1H-pyrazole-4-carboximidohydrazide recyclizes to give compound 10. Thermodynamic parameters for the hydrazine-promoted transformation of

• calculations was proposed. It involves nucleophilic attack of hydrazine on the C2 carbon of the pyrimidine ring followed by cleavage of the C2–N3 bond, dimerization of the bis-amidrazone formed, and macrocyclization of the dimer. The DFT calculations also showed that the hydrazine-promoted transformation of

Benzoimidazolium-derived dimeric and hydride n-dopants for organic electron-transport materials: impact of substitution on structures, electrochemistry, and reactivity

• Swagat K. Mohapatra,
• Khaled Al Kurdi,
• Samik Jhulki,
• Georgii Bogdanov,
• John Bacsa,
• Maxwell Conte,
• Tatiana V. Timofeeva,
• Seth R. Marder and
• Stephen Barlow

Beilstein J. Org. Chem. 2023, 19, 1651–1663, doi:10.3762/bjoc.19.121

• 1g2 exhibit weaker bonds than 1e2 and 1h2 and thus react with 6,13-bis(triisopropylsilylethynyl)pentacene (VII) via a “cleavage-first” pathway, while 1e2 and 1h2 react only via “electron-transfer-first”. 1h2 exhibits the most cathodic E(12•+/12) value of the dimers considered here and, therefore

• previously reported for the Y = cyclohexyl, R = R' = H derivative 1e2 (1.640(4) Å) [14], despite DFT calculations indicating that the former dimer is considerably more weakly bonded [8][14] and kinetic evidence for the “cleavage-first” mechanism occurring in doping reactions using 1b2 but not 1e2 (see below

• electrochemical section; however, the observed rate constants for 1bH and 1iH suggest that 5-dimethylamino-2-thienyl affords less net charge stabilization than 4-dimethylaminophenyl. Two reaction pathways have been established for the oxidation of organometallic and organic dimers. A “cleavage-first” mechanism

Synthesis and biological evaluation of Argemone mexicana-inspired antimicrobials

• Jessica Villegas,
• Bryce C. Ball,
• Katelyn M. Shouse,
• Caleb W. VanArragon,
• Ashley N. Wasserman,
• Hannah E. Bhakta,
• Allen G. Oliver,
• Danielle A. Orozco-Nunnelly and
• Jeffrey M. Pruet

Beilstein J. Org. Chem. 2023, 19, 1511–1524, doi:10.3762/bjoc.19.108

• nevertheless successful, albeit in low yields after an extended reaction time. We explored KOH and NH3 as alternatives to NaOH for this amide cleavage, and found the resulting yields less satisfactory. We also explored the amide hydrolysis under acidic conditions as well, though this resulted to almost

Unraveling the role of prenyl side-chain interactions in stabilizing the secondary carbocation in the biosynthesis of variexenol B

• Moe Nakano,
• Rintaro Gemma and
• Hajime Sato

Beilstein J. Org. Chem. 2023, 19, 1503–1510, doi:10.3762/bjoc.19.107

• bond length. Judging from the bond length alone, it is not impossible to conclude that the C10–C14 bond is formed, but considering the rational mechanism of organic reactions, bond cleavage does not occur immediately after the bond is formed. On the other hand, the C10–C14 bond length of IM2b is 1.64 Å

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

• sulfur atom to Fe3+ to generate Fe2+ and radical cation I. Subsequent cleavage of the N–S bond led to cation II and radical III. Interaction of III with Fe2+ regenerated the Fe3+ species and IV. At the same time, electrophilic addition of II to alkene 9 yielded intermediate V, which was subjected to the

• efficient Lewis acid catalyst (Scheme 10) [50]. In the procedure, oxidative cleavage of one S–N bond and 1,2-sulfur migration afforded π-conjugated 6-substituted 2,3-diarylbenzo[b]thiophenes 16. A plausible mechanism is shown in Scheme 11. The coordination of AlCl3 with the phthalimide/succinimide unit of 1

• dihydropyrazoles 54 as products (Scheme 22) [59]. A credible pathway for the production of isoxazole 53 is illustrated in Scheme 23. The interaction of 1 with BF3·Et2O resulted in intermediate I that is in balance with I’. Cleavage of the N–S bond of I afforded cationic species PhS+ II, which activated the double

One-pot nucleophilic substitution–double click reactions of biazides leading to functionalized bis(1,2,3-triazole) derivatives

• Hans-Ulrich Reissig and
• Fei Yu

Beilstein J. Org. Chem. 2023, 19, 1399–1407, doi:10.3762/bjoc.19.101

• carbohydrate mimetics, but the reductive cleavage of the 1,2-oxazine rings to aminopyran moieties did not proceed cleanly with these compounds. Keywords: alkynes; azides; copper catalysis; nucleophilic substitution; 1,2-oxazines; Introduction The concept of click reactions [1][2], in particular, the

• on carbon and provided the expected (propyloxy)methyl-substituted aminopyran 22 in 81% yield (Scheme 7, reaction 1). The reductive removal of the N-benzyl group and the cleavage of the N–O bond occurred apparently without problems. With the second model compound, 1,2,3-triazole 23, which is almost

• other triazolyl-substituted aminopyran derivatives we encountered similar selectivity problems due to the sensitivity of benzylic bonds to the applied hydrogenolysis conditions [59]. Despite of the discouraging results with model compound 23 we nevertheless examined the reductive cleavage of bis(1,2,3

Synthesis of ether lipids: natural compounds and analogues

• Marco Antônio G. B. Gomes,
• Alicia Bauduin,
• Chloé Le Roux,
• Romain Fouinneteau,
• Wilfried Berthe,
• Mathieu Berchel,
• Hélène Couthon and
• Paul-Alain Jaffrès

Beilstein J. Org. Chem. 2023, 19, 1299–1369, doi:10.3762/bjoc.19.96

• reported by H. Eilb [72]. Accordingly, ᴅ-mannitol was transformed in 1,2,5,6-diisopropylidene-ᴅ-mannitol (4.2) by reaction with acetone and ZnCl2. Of note, compound 4.2 was isolated with 5–10% of 1,2,3,4,5,6-triisopropylidene-ᴅ-mannitol. The oxidative cleavage of 4.2 with sodium periodate yields 4.3 that

• intermediate 6.3 (ᴅ- or ʟ-threitol) that was then alkylated with mesityl lipid alcohol to produce 6.4 [80][81]. The acetal protecting group was removed in acidic conditions and then the intermediate 6.5 was subjected to oxidative cleavage to yield an aldehyde that was reduced with NaBH4 to produce 6.6a,b

• followed by the methylation with iodomethane. Then, the cleavage of the acetal occurs by reaction with BH3·THF to give 24.3. Then, the primary alcohol was alkylated with the lipid chain (e.g., C16H33) to produce 24.4. Finally, the benzyl protecting group was removed by catalytic hydrogenolysis to produce

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

• , and the cleavage of the C(sp3)–H bond in the ether substrates which produces α-alkyl radicals is the rate-determining step. Fe-catalyzed reactions Iron is a transition metal with abundant reserves, low price, and non-toxicity, which shows many characteristics in catalytic processes, such as the

• of ethers to obtain symmetric and asymmetric 1,1-bis-indolylmethane derivatives (Scheme 23) [84]. The reaction proceeds through the tandem oxidative coupling of the C–O bond and cleavage of the C–H bond. Fe plays a dual role in catalysing the C–C bond coupling and C–O bond cleavage as Lewis acid

• the reaction mechanism supported by DFT calculations and concluded that FeF2 plays an important redox role in assisting the cleavage of oxidants and the oxidation of carbon radicals to cationic intermediates of oxygen. CDC reactions between C(sp3)–H/C(sp)–H bonds catalyzed by iron have been reported

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

• ). Notably, the protocol was also applicable to 4-iodotoluene as a moderately deactivated aryl iodide and the C(sp2)–I bond cleavage occurred chemoselectively in the presence of a C(sp2)–Br bond. N-Methylpyrrole and various other substituted pyrroles could be applied as trapping agents for electron-poor aryl

• the single electron reduction of aryl halides while simultaneously generating S4•−. Upon C(sp2)–X bond cleavage, an aryl radical is formed and trapped by a trapping reagent such as N-methylpyrrole, yielding the open-shell species 4•. Upon irradiation of S3•−, the excited species *[S3•−] oxidizes 4• to

• (PCET) from [Ir2]+ could not be ruled out. With no trapping reagents or further reactants present, the aryl radicals generated by C(sp2)–X bond cleavage yield hydrodehalogenated products 2 via HAT. Under irradiation with blue light, [Ir2]0 was found to reduce a variety of aryl halides to their

Synthesis of imidazo[4,5-e][1,3]thiazino[2,3-c][1,2,4]triazines via a base-induced rearrangement of functionalized imidazo[4,5-e]thiazolo[2,3-c][1,2,4]triazines

• Dmitry B. Vinogradov,
• Alexei N. Izmest’ev,
• Angelina N. Kravchenko,
• Yuri A. Strelenko and
• Galina A. Gazieva

Beilstein J. Org. Chem. 2023, 19, 1047–1054, doi:10.3762/bjoc.19.80

• in the thiazine ring leads to the cleavage of the triazine C–N bond. Further proton transfer gives product 9. The structures of the synthesized compounds 3a,b,j and 5a–k,m were confirmed by IR, 1H and 13C NMR spectroscopy, and high-resolution mass spectrometry. the potassium salts 3c–i,k,m were

Linker, loading, and reaction scale influence automated glycan assembly

• Marlene C. S. Dal Colle,
• Manuel G. Ricardo,
• Nives Hribernik,
• José Danglad-Flores,
• Peter H. Seeberger and
• Martina Delbianco

Beilstein J. Org. Chem. 2023, 19, 1015–1020, doi:10.3762/bjoc.19.77

• glycan sequences. We showed that, while loading and reaction scale did not significantly influence the AGA outcome, the chemical nature of the linker dramatically altered the isolated yields. We identified that the major determinants of AGA yields are cleavage from the solid support and post-AGA

• light (λ = 360 nm), L1 releases the glycan equipped with an aminoalkyl spacer at the reducing end, whereas L2 affords the free reducing sugar (α/β mixture). Previous data suggested that UV cleavage of L1 and L2 was equally efficient, permitting the isolation of a tetramannoside in around 60% yield [3

• cleavage is probably influenced by glycan structure, solubility, and aggregation tendency [26]. Lastly, purification of the protected glycan upon cleavage could be affected by the presence or absence of a linker. L1 or L2 were conjugated to Merrifield resins with initial loadings of 0.5 mmol/g and 1.0 mmol

Aromatic C–H bond functionalization through organocatalyzed asymmetric intermolecular aza-Friedel–Crafts reaction: a recent update

• Anup Biswas

Beilstein J. Org. Chem. 2023, 19, 956–981, doi:10.3762/bjoc.19.72

• stereoselectivity is also explained. Keywords: asymmetric; aza-Friedel–Crafts reaction; H-bonding; organocatalysis; stereoselectivity; Introduction The ease of a chemical transformation depends on the thermodynamic instability of a chemical bond owing to its fast cleavage under mild reaction conditions. A C–H

• different types of C–H bonds, an aromatic C–H bond is even more inert rendering this type of bond functionalization more difficult. Herewith the term “bond functionalization” is defined as the cleavage of an existing bond with substitution by another bond. Aromatic C–H bond functionalizations have gained

• reactivity of catalyst P5 initiated with the protonation of amidates 42 to generate intermediate 44 through ring cleavage. Then, the intermediate 44 was paired with the anionic conjugate base of catalyst P5 and acts as electrophile to facilitate the conjugate Friedel–Crafts reaction involving C3 of indole 4

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

• easily generate reactive open-shell radical species and/or intermediates. The substrate is consequently activated for bond cleavage, atom abstraction, or nucleophilic or electrophilic attack. After quenching, the oxidized or reduced photocatalyst regains or loses an electron to return to the starting