Carbonylative synthesis and functionalization of indoles

• Alex De Salvo,
• Raffaella Mancuso and
• Xiao-Feng Wu

Beilstein J. Org. Chem. 2024, 20, 973–1000, doi:10.3762/bjoc.20.87

• , Davies et al. published a paper presenting a new method for the synthesis of indoles from o-nitrostyrenes by using a different catalyst system and performing the reaction under mild conditions [27]. At first they decided to change the catalytic system applied by Söderberg using 1,10-phen instead of PPh3

• and, in terms of gas pressure, took place under mild conditions comparable to the ones reported by Xu et al. (Scheme 31). Chandrasekhar and Sankararaman also tested primary amines under the conditions outlined in Scheme 31, however, the reaction gave the annulated products (as the secondary amines

• by Li et al. [68]. The process occurred under mild conditions (such as the approaches seen above) under 1 bar of CO, in DMF or CH3CN, at 80–100 °C for 24–48 h. In addition to 5 mol % of Pd(OAc)2, 3 equiv of K2CO3 and 2.5 equiv of I2 were added. The reactions were carried out by using both aliphatic

Advancements in hydrochlorination of alkenes

• Daniel S. Müller

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

• , terminal aliphatic alkenes can now be hydrochlorinated under mild conditions at room temperature. The industrial application of this reaction by Merck underscores its practical utility for pharmaceutical production. While high functional group tolerance is achievable for polar hydrochlorinations with

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

• limitation of the photoinduced palladium-catalyzed carboamination reactions and the radical-mediated difunctionalization of alkenes with diazo compounds. We envisioned an interesting MCR strategy with mild conditions to access unsaturated γ- and ε-AA derivatives via a π-allyl Pd radical-polar crossover

• also compatible with these mild conditions (4y–aa, 51–72%). Additionally, the diazo derivative of epiandrosterone was reactive in this protocol, giving the product 4ab in 59% yield. Delightedly, this procedure was successfully applied to aromatic amine (N-methylaniline), primary amine (aniline) and

Synthesis and biological profile of 2,3-dihydro[1,3]thiazolo[4,5-b]pyridines, a novel class of acyl-ACP thioesterase inhibitors

• Jens Frackenpohl,
• David M. Barber,
• Guido Bojack,
• Birgit Bollenbach-Wahl,
• Ralf Braun,
• Rahel Getachew,
• Sabine Hohmann,
• Kwang-Yoon Ko,
• Karoline Kurowski,
• Bernd Laber,
• Rebecca L. Mattison,
• Thomas Müller,
• Anna M. Reingruber,
• Dirk Schmutzler and
• Andrea Svejda

Beilstein J. Org. Chem. 2024, 20, 540–551, doi:10.3762/bjoc.20.46

• proceeded cleanly under mild conditions, using the corresponding acyl chloride together with triethylamine as a suitable base in DCM. Furthermore, we evaluated the tolerance of [1,3]thiazolo[4,5-b]pyridines 12a–c, containing a bromine atom, towards the optimized B(C6F5)3-mediated reduction. In good

• ]pyridine (13c, 54% combined isolated yield). As shown for N-acylated target compounds 16a–f, the acylation of 6-bromo-2,3-dihydro[1,3]thiazolo[4,5-b]pyridines 13a–c, affording target compounds 14a–c, proceeded under mild conditions with a suitable acyl chloride reagent and triethylamine as base in DCM. It

Green and sustainable approaches for the Friedel–Crafts reaction between aldehydes and indoles

• Periklis X. Kolagkis,
• Eirini M. Galathri and
• Christoforos G. Kokotos

Beilstein J. Org. Chem. 2024, 20, 379–426, doi:10.3762/bjoc.20.36

Nucleophilic functionalization of thianthrenium salts under basic conditions

• Xinting Fan,
• Duo Zhang,
• Xiangchuan Xiu,
• Bin Xu,
• Yu Yuan,
• Feng Chen and
• Pan Gao

Beilstein J. Org. Chem. 2024, 20, 257–263, doi:10.3762/bjoc.20.26

• introduced a pioneering method for synthesizing air- and moisture-stable arylthianthrenium salts [11]. This novel approach involves the utilization of tetra-fluorothianthrene sulfoxide (TFT=O) or thianthrene sulfoxide (TT=O), which react with arenes under mild conditions, exhibiting exclusive

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

• pyridine rings, the naphthalene core at positions 5(8) and the CH2CH2 bridge (dehydrogenation) undergo chemical modifications under mild conditions, giving the corresponding acenaphthylenes. The latter can also be obtained in an unusual way by tele-elimination from 5,8-dibromodipyridoacenaphthene by

• -stacking of almost planar diazaarene fragments, leading to pronounced supramolecular aggregation. Although dipyridoacenaphthene does not undergo nucleophilic amination and dehydrogenation under a wide range of conditions, its 5(8)-nitro derivatives can be transformed under mild conditions into the

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

• , leading to the formation of the α-phosphoryl GlcNAc-MurNAc-monopeptide derivative. Subsequently, coupling this intermediate with tetrapeptide, TFA·H-ʟ-Ala-γ-ᴅ-Glu(OMe)-ʟ-Lys(COCF3)-ᴅ-Ala-ᴅ-Ala-OMe under mild conditions resulted in the synthesis of dibenzyl α-phosphoryl GlcNAc-MurNAc-pentapeptide 7 (see

Copper-catalyzed multicomponent reaction of β-trifluoromethyl β-diazo esters enabling the synthesis of β-trifluoromethyl N,N-diacyl-β-amino esters

• Youlong Du,
• Haibo Mei,
• Ata Makarem,
• Ramin Javahershenas,
• Vadim A. Soloshonok and
• Jianlin Han

Beilstein J. Org. Chem. 2024, 20, 212–219, doi:10.3762/bjoc.20.21

• -catalyzed conditions has been developed, which affords various unsymmetrical β-trifluoromethyl N,N-diacyl-β-amino esters in good to excellent yields. The reaction features mild conditions, a wide scope of β-amino esters and carboxylic acids, and also applicability to large-scale synthesis, thus providing an

• diacyl β-amino esters can be easily constructed with good chemical yields. The reaction is conducted under mild conditions and shows good applicability to different series of substrates, which provides an efficient way for the preparation of unsymmetric trifluoromethyl diacyl β-amino esters. Experimental

• undergo a Mumm rearrangement to provide unsymmetrical β-trifluoromethyl diacyl-β-amino esters as products (Scheme 1c). Herein, we report our results on the design of β-trifluoromethyl β-diazo esters and their application in a three-component reaction with nitriles and carboxylic acids under mild

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

• reactions. Highly nucleophilic arenes like 1,3,5-trimethoxybenzene react easily under mild conditions and result in a stabilized benzylic cation in acidic conditions, allowing a second intramolecular Friedel–Crafts reaction involving the aryl substituent of the substrate. These reactions are favored by π

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

Visible-light-induced radical cascade cyclization: a catalyst-free synthetic approach to trifluoromethylated heterocycles

• Chuan Yang,
• Wei Shi,
• Jian Tian,
• Lin Guo,
• Yating Zhao and
• Wujiong Xia

Beilstein J. Org. Chem. 2024, 20, 118–124, doi:10.3762/bjoc.20.12

• usually occur under mild conditions, they typically require expensive metal-based photocatalysts or structurally complex organic dyes [18]. Therefore, the development of a photoinduced cascade reaction without the need of additional catalysts or additives remains highly desirable [19]. The introduction of

• to furnish trifluoromethylated dihyropyrido[1,2-a]indolones under mild conditions, without the need of photocatalysts or transition metals [28]. Results and Discussion We initialized our study by employing Ru(bpy)3Cl2·6H2O and Umemoto’s reagent to generate trifluoromethyl radicals via a photo

1-Butyl-3-methylimidazolium tetrafluoroborate as suitable solvent for BF₃: the case of alkyne hydration. Chemistry vs electrochemistry

• Marta David,
• Elisa Galli,
• Richard C. D. Brown,
• Marta Feroci,
• Fabrizio Vetica and
• Martina Bortolami

Beilstein J. Org. Chem. 2023, 19, 1966–1981, doi:10.3762/bjoc.19.147

• examples of the hydration reaction of alkynes carried out in ILs. In one case, a dicationic IL, containing sulfuric acid as catalyst, was used as reaction medium to carry out the hydration of different alkynes under mild conditions (40–60 °C, 0.5–1 h) [84]. In a second case, different Brønsted acid ionic

Construction of diazepine-containing spiroindolines via annulation reaction of α-halogenated N-acylhydrazones and isatin-derived MBH carbonates

• Xing Liu,
• Wenjing Shi,
• Jing Sun and
• Chao-Guo Yan

Beilstein J. Org. Chem. 2023, 19, 1923–1932, doi:10.3762/bjoc.19.143

• readily available reagents, mild conditions, satisfactory yields, broad substrate scope, high molecular convergence, and atomic economy. The synthetic applications of this annulation reaction in heterocyclic chemistry might be significant. Experimental General procedure for the preparation of dihydrospiro

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

• -phenylpyrazolin-3-one, an exceptionally low conversion of the starting heterocycle was observed. In the next step, we have demonstrated the possibility of removing the protective Boc group under mild conditions without acid or base catalysis (Scheme 4). Deprotection occurs in high, near quantitative yields

• the preparation of modified glutarimides with a wide range of aromatic and aliphatic NH-heterocycles under mild conditions in moderate to high yields. It is shown that electron-rich substrates tend to give C–H insertion products. The N-modification of tetrazoles and 1,2,4-triazoles using a

Synthetic approach to 2-alkyl-4-quinolones and 2-alkyl-4-quinolone-3-carboxamides based on common β-keto amide precursors

• Yordanka Mollova-Sapundzhieva,
• Plamen Angelov,
• Danail Georgiev and
• Pavel Yanev

Beilstein J. Org. Chem. 2023, 19, 1804–1810, doi:10.3762/bjoc.19.132

• ≤ 0.78 µg/mL for levofloxacin as the positive control. Conclusion In conclusion, we have demonstrated that β-keto amides and 2-nitrobenzoyl chloride can be used as convenient precursors to a variety of 4-quinolone derivatives. The described approach is realized in a small number of steps, under mild

• conditions, and allows easy installation of long-chain substituents at the C-2 position of the quinolone core. These characteristics of the synthetic method could be particularly attractive in the search of novel mimics of the Pseudomonas quorum-sensing signal molecules. The high activity of compounds 4d and

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

• weight. The simple setup, mild conditions, absence of unfavored byproducts, orthogonality with other reactions, and high yields (nearly full conversion) [82] made thiol–ene polymerizations an ideal way to produce high-molecular-weight cross-linked polymers, optical polymers, biomacromolecules, and

• molecules were recovered at a yield of ≈40% and ≈20%, respectively. Both processes were carried out under relatively mild conditions, paving a route toward a greener future of vinyl polymer upcycling. However, the yield and value of the small molecules produced in photooxidative depolymerization are still

Morpholine-mediated defluorinative cycloaddition of gem-difluoroalkenes and organic azides

• Tzu-Yu Huang,
• Mario Djugovski,
• Sweta Adhikari,
• Destinee L. Manning and
• Sudeshna Roy

Beilstein J. Org. Chem. 2023, 19, 1545–1554, doi:10.3762/bjoc.19.111

• -promoted [22] azide–alkyne cycloaddition reactions [17][23][24]; however, most of these strategies use high temperatures [21][25]. Herein, we report the discovery of a novel, one-step regioselective method under mild conditions to obtain 1,4,5-trisubstituted-1,2,3-triazoles from gem-difluoroalkenes

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

• pyrazolone derivatives with N-thiophthalimides catalyzed by 1 mol % of chiral iminophosphorane organocatalyst was carried out under mild conditions [103]. Solvent control in the procedure can affect the yield of products due to the solubility of the catalysts. Various solvents, such as acetone, ethyl acetate

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

• carbonyl compounds to provide the corresponding zinc enolates (Scheme 1) [1][2]. While simple, this reaction offers attractive features: 1) it proceeds under mild conditions in the absence of any transition-metal catalyst; 2) the 1,4-addition step can be combined with condensation reactions of the zinc

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

• might be feasible. Herein, we disclose a visible-light-induced nickel-catalyzed cross-coupling of alkyl carboxylic acids with N-trifluoroethoxyphthalimide to deliver trifluoromethyl aliphatic acyloins under mild conditions (Scheme 1d). Furthermore, this platform bypasses the need for exogenous

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

• mild conditions the benzylation of the alcohol function to yield 7.3. Then, the removing of the tosyl group required a two-step sequence. First, 7.3 reacted with cesium acetate and then the resulting ester was reduced with LiAlH4 to produce 7.4 with control of its stereochemistry. Very recently, a new

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

• ether α-C–H bond. In the presence of Cu(II), the C(sp2)–C(sp3) coupling of pyridine N-oxides and coumarins with cyclic ethers could be achieved under mild conditions (Scheme 13) [63][64]. These reactions do not all follow the reaction mechanism of the oxidative olefination of simple ethers. The role of

• -chain alkyl ethers in the presence of DBU under relatively mild conditions (Scheme 29b) [92]. In 2018, Wang et al. developed the cobalt-catalyzed oxidative CDC reaction of 2-arylimidazo[1,2-a]pyridines with isochroman using molecular oxygen as an oxidant (Scheme 30) [93]. These reactions involved a

• oxidant (Scheme 38a) [103]. Subsequently, Li et al. developed the CDC of heterocyclic aromatics with simple ethers mediated by AgOTFA to construct C(sp2)–C(sp3) bonds. The reaction proceeds under mild conditions (room temperature) with a wide range of substrates (Scheme 38b) [104]. The reaction mechanism

Exploring the role of halogen bonding in iodonium ylides: insights into unexpected reactivity and reaction control

• Carlee A. Montgomery and
• Graham K. Murphy

Beilstein J. Org. Chem. 2023, 19, 1171–1190, doi:10.3762/bjoc.19.86

• reported by Hadjiarapoglou, Varvoglis and co-workers [107][108][109][110][111][112] and Moriarty et al. [113][114][115], who observed metal-free cycloadditions between iodonium ylides and olefins in the absence of a transition metal catalyst. These reactions proceeded under mild conditions without catalyst

• produced in 74% yield after six days at room temperature in the absence of catalyst (Scheme 2a) [107]. At that time, the authors did not articulate any theory as to how the reaction might initiate under such mild conditions, though they recognized that the decomposition of 8 into a free carbene would not

• intermediate was not viable under such mild conditions. The initially proposed ionic pathway (Figure 5, left) was abandoned as solvent effects had little influence on the reaction rate, and since no Wagner–Meerwein rearrangement products were detected with bicyclic olefin precursors. Radical-based pathways

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

• intermediates under mild conditions for both oxidative and reductive reactions and ii) to use photons as traceless reagents to drive reactions in a “greener” manner [1][2][3][4][5][6]. As depicted in Figure 1, for an oxidative PRC cycle, the excited photocatalyst (*PC) firstly undergoes oxidative quenching by

• 2.1.1 C(sp2)–X activation: In the rise of visible light-mediated PRC, the generation of aryl radicals for C(sp2)–C(sp2/3) couplings under mild conditions (room temperature, visible light activation of a catalyst) was heavily investigated [34][35][36]. However, initially the procedures were generally