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

• carbon monoxide insertion, and Suzuki–Miyaura coupling reaction, from 2-gem-dibromovinylaniline [12]. In the presence of Pd(PPh3)4 (5 mol %) as catalyst, 5 equivalents of base (K2CO3), an aryl- or heteroarylboronic ester (1.1 equivalents), CO (12 bar), in dioxane at 100 °C after 16 h the indole

• indoles Metal-catalyzed cyclocarbonylative coupling reaction of indoles to 6H-isoindolo[2,1-a]indol-6-one scaffolds Substituted 6H-isoindolo[2,1-a]indol-6-ones are important structural components of many naturally occurring and pharmacologically active compounds [45][46][47][48][49][50][51]. They are also

• , the Li’s group and Zeng and Alper developed two different methods for carrying out a direct carbonylation of indoles with alkynes. Li’s group reported the direct Sonogashira carbonylation coupling reaction of indoles and alkynes catalyzed by Pd/CuI in the presence of iodine as oxidant [71]. The

Synthesis and characterization of water-soluble C₆₀–peptide conjugates

• Yue Ma,
• Lorenzo Persi and
• Yoko Yamakoshi

Beilstein J. Org. Chem. 2024, 20, 777–786, doi:10.3762/bjoc.20.71

• NMM (8 equiv) in DMF. Each Fmoc deprotection step of the peptide N-terminus was conducted by the repeated treatment of the peptide on resin with 20% piperidine in DMF (2 × 10 min). After each coupling reaction, the resin was washed with DMF. Synthesis of C60–peptide conjugates 5a–c The synthetic

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

• co-workers reported that the combination of NHPI esters and cesium carbonate (Cs2CO3) gave rise to a new absorption band in the visible region, suggesting the formation of a photoactive charge-transfer complex [70]. This activation mode was initially employed in a decarboxylative coupling reaction

• the three-component alkylacylation of olefins [108]. Alternatively, NHC catalysts can mediate the generation of radical intermediates from NHPI esters via the stabilization of a photoactive EDA complex. In 2020, Wang and Chen reported a photochemical C(sp3)-heteroatom coupling reaction of NHPI esters

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

• mixture underwent a cross-coupling reaction with prenyl monophosphates [46] in DMF/THF over a four-day period, yielding fully protected versions of lipid II and its analogues. Subsequent global deprotection reactions, using aqueous NaOH, led to the formation of lipid II (11), with an overall yield of 16

Metal-catalyzed coupling/carbonylative cyclizations for accessing dibenzodiazepinones: an expedient route to clozapine and other drugs

• Amina Moutayakine and
• Anthony J. Burke

Beilstein J. Org. Chem. 2024, 20, 193–204, doi:10.3762/bjoc.20.19

• approaches resulted in shortening the synthetic routes that were widely employed to access these heterocyclic scaffolds. Over the last decades, the Chan–Lam coupling reaction has drawn great attention among the synthetic chemistry community which contributed to the development of various synthetic routes to

• via a cross-coupling reaction with NH3 [13]. The reaction was undertaken in the presence of a catalytic amount of a palladium catalyst and afforded a library of dibenzodiazepinones in good to excellent yields (Scheme 1a). In 2013, Zhang et al. developed a synthetic route leading to structurally

• , the desired intermediate 3a was obtained in 20% yield along with 55% of the phenazine 6 (entry 14, Table 2). Although toluene was shown to be a good solvent for this B–H coupling reaction, we were unable to prevent the double B–H reaction from occurring leading to the phenazine 6, even when shortening

Multi-redox indenofluorene chromophores incorporating dithiafulvene donor and ene/enediyne acceptor units

• Christina Schøttler,
• Kasper Lund-Rasmussen,
• Line Broløs,
• Philip Vinterberg,
• Ema Bazikova,
• Viktor B. R. Pedersen and
• Mogens Brøndsted Nielsen

Beilstein J. Org. Chem. 2024, 20, 59–73, doi:10.3762/bjoc.20.8

• a subsequent Glaser–Hay coupling reaction, a RA acceptor unit was introduced to provide a DTF-IF-RA donor–acceptor scaffold with a low-energy charge-transfer absorption and multi-redox behavior. Keywords: alkynes; chromophores; fused-ring systems; heterocycles; redox chemistry; Introduction

Biphenylene-containing polycyclic conjugated compounds

• Cagatay Dengiz

Beilstein J. Org. Chem. 2023, 19, 1895–1911, doi:10.3762/bjoc.19.141

• the synthesis of compound 81 through the utilization of the Negishi cross-coupling reaction and then the removal of TMS groups from this intermediate was achieved using TBAF, resulting in the formation of diyne 82 in 65% yield. The progression towards the synthesis of biphenylene-containing substrate

• selectively synthesize compound 87 through a hybrid approach involving the integration of both solution and surface chemistry techniques [53]. The key compound 96 to be used in the synthesis of POA 87 was synthesized in two steps. In the first step, 94 was obtained using a double Sonogashira cross-coupling

• reaction, followed by a Au(I)-catalyzed [4 + 2] cycloaddition reaction to afford the target substrate 96 and its regioisomer 95 in a 2:1 ratio (Scheme 20). POA 87 was obtained on Au(111) at 610 K after Ullmann-type coupling and aromatic dehydrogenation of compound 96. Apart from these studies, the

Controlling the reactivity of La@C₈₂ by reduction: reaction of the La@C₈₂ anion with alkyl halide with high regioselectivity

• Yutaka Maeda,
• Saeka Akita,
• Mitsuaki Suzuki,
• Michio Yamada,
• Takeshi Akasaka,
• Kaoru Kobayashi and
• Shigeru Nagase

Beilstein J. Org. Chem. 2023, 19, 1858–1866, doi:10.3762/bjoc.19.138

• derivatives followed by the radical coupling reaction is more plausible for the formation of the corresponding adducts rather than the SN2 reaction mechanism of the La@C2v-C82 anion with benzyl bromide derivatives. Conclusion The reaction of La@C2v-C82 anion with benzyl bromide derivatives 1 at 110 °C

Thienothiophene-based organic light-emitting diode: synthesis, photophysical properties and application

• Recep Isci and
• Turan Ozturk

Beilstein J. Org. Chem. 2023, 19, 1849–1857, doi:10.3762/bjoc.19.137

• 4-bromo-N,N-diphenylaniline (5) with n-butyllithium at −78 °C and addition of 2-isopropoxy-4,4,5,5-tetramethyl-1,3,2-dioxaborolane. The Suzuki-coupling reaction of TT 4 with borolane 6 produced the intermediate 7 in 81% yield. The target D–π–A-type fluorophore, DMB-TT-TPA (8), was produced by

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

• -mediated domino reaction of chromone-3-carboxaldehydes and amines [41], Pd-catalyzed redox-neutral C–N coupling reaction of iminoquinones with electron-deficient alkenes [42], NH3 insertion into o‑haloarylynones [43], gold(III)-catalyzed azide-yne cyclization [44], Michael/Truce-Smiles rearrangement

Active-metal template clipping synthesis of novel [2]rotaxanes

• Cătălin C. Anghel,
• Teodor A. Cucuiet,
• Niculina D. Hădade and
• Ion Grosu

Beilstein J. Org. Chem. 2023, 19, 1776–1784, doi:10.3762/bjoc.19.130

• the reaction used to complete rotaxane synthesis, hence the name “active template”. This strategy was first applied by Saito and co-workers [35], using a Cu(I) template to catalyze a Glaser coupling reaction. The method has been extended for other reactions, for example Ni-catalyzed homocoupling of

Trifluoromethylated hydrazones and acylhydrazones as potent nitrogen-containing fluorinated building blocks

• Zhang Dongxu

Beilstein J. Org. Chem. 2023, 19, 1741–1754, doi:10.3762/bjoc.19.127

• -withdrawing property of the trifluoromethyl group is key to this coupling reaction [45] (Scheme 7). Trifluoromethylated hydrazonoyl halides Hydrazonoyl halides, which offer a reactive 1,3-dipole, can easily be transformed to nitrile imines in the presence of a base, and they have shown to be useful building

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

• OLED realized a maximum external quantum efficiency (EQEmax) of 3.32% with an emission peak at 659 nm. Results and Discussion The designed TPECNz molecule was synthesized by a multistep reaction as described in Scheme 1. Initially, an Ullmann coupling reaction of bromo-TPE 1 and carbazole provided TPE

• )diboron catalyzed by Pd(dpf)Cl2/KOAc. Finally, TPECNz was obtained as red solid in a reasonable yield by a Suzuki-type cross-coupling reaction between 3 and 4,9-dibromonaphtho[2,3-c][1,2,5]thiadiazole. The chemical structure and purity of compound 3 were verified by 1H NMR, 13C NMR, and high-resolution

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

• ]. The semiquinone radicals formed during the oxidation of catechol can undergo a cross-coupling reaction to form polymers (Scheme 1). One example is the radical polymerization of urushiol. The earliest recorded application of natural radical polymerization can be traced back to the manufacture of

• inert substrates. Here, radical chemistry comes into play. When polymer surfaces are modified by radical chemistry, radicals are either generated directly on the polymers or on modifiers. In the latter case, a radical addition, substitution, or coupling reaction takes place to complete the modification

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

• sulfide moieties 11 was performed by Fu et al. (Scheme 6) [47]. Iron(III) chloride was used as a catalyst for this coupling reaction without the need of any ligand and additive. Screening for other metal salts, such as Cu(OAc)2, Pd(OAc)2, AgOAc or CuI was not successful, although FeS·7H2O, FeS, Fe2(SO4)3

• as a sulfenylating source gave the target product in 93% yield. Knochel and co-workers found that copper acetate can catalyze the cross-coupling reaction between (hetero)aryl, alkyl and benzylic zinc halides 36 with N-thiophthalimides 14 (Scheme 18) [55]. Various metal catalysts, including CrCl2

• , CoCl2, NiCl2, MnCl2, FeCl2, Fe(acac)3 and copper salts such as Cu(OAc)2, CuBr2, CuBr, CuCl2, and CuCN·2LiCl were evaluated in this coupling reaction, in which Cu(OAc)2 showed highest product yields. Moreover, phthalimides with SCF3, SCN, and SePh groups also worked well in this approach. Because of the

Application of N-heterocyclic carbene–Cu(I) complexes as catalysts in organic synthesis: a review

• Nosheen Beig,
• Varsha Goyal and
• Raj K. Bansal

Beilstein J. Org. Chem. 2023, 19, 1408–1442, doi:10.3762/bjoc.19.102

• conditions, although the transition-metal catalysts were preserved, the reactions require high temperature conditions [76]. In 2008, Wang and co-workers [77] for the first time employed an NHC–Cu(I) complex (2 mol %) and its silica-immobilized version 141 (2 mol %) as catalyst for an A3 coupling reaction

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

• complex between Hantzsch ester and N-trifluoroethoxyphthalimide was subsequently engaged in a nickel-catalyzed coupling reaction with in situ-activated alkyl carboxylic acids. This convenient protocol does not require photocatalysts and metal reductants, providing a straightforward and efficient access to

• the substrate scope of this photoinduced nickel-catalyzed cross coupling reaction. As illustrated in Scheme 2, a broad array of aliphatic carboxylic acids reacted smoothly in this protocol, providing the corresponding trifluoromethyl aliphatic acyloins in moderate to excellent yields. This mild

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

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

• oxidative alkylation of cyclic benzyl ethers with malonates or ketones. Oxygen is used as a terminal oxidant at atmospheric pressure. The key intermediate of this oxidative coupling reaction is benzyl alcohol intermediate C (Scheme 4) [52]. The generation of N–O radicals from NHPI in the presence of oxygen

• triggers the whole coupling reaction. The potential application of NHIP as a catalyst for oxidative coupling reactions with oxygen as a terminal oxidant was explored. In 2011, Garcia-Mancheño et al. developed a Cu-catalyzed CDC of cyclic benzyl ethers 10 with aliphatic or α,β-unsaturated aldehydes 13 or 14

• , tetrahydrofuran or tetrahydropyran can smoothly react with many methyl aryl ketones to obtain the desired coupling products (Scheme 6a) [54]. The mechanism of the dehydrogenation cross-coupling reaction may undergo a radical pathway. Initially, the tert-butoxy radical produced by the dissociation of t-BuOOH may

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

The effect of dark states on the intersystem crossing and thermally activated delayed fluorescence of naphthalimide-phenothiazine dyads

• Liyuan Cao,
• Xi Liu,
• Xue Zhang,
• Jianzhang Zhao,
• Fabiao Yu and
• Yan Wan

Beilstein J. Org. Chem. 2023, 19, 1028–1046, doi:10.3762/bjoc.19.79

• chromophores, which are coupled through a Buchwald–Hartwig coupling reaction (another NI-PTZ paper) [39]. The oxidation of the PTZ unit was readily performed by treatment with H2O2 as oxidant (Scheme 1). All compounds were obtained with satisfactory yields and the molecular structures were fully characterized

Synthesis of aliphatic nitriles from cyclobutanone oxime mediated by sulfuryl fluoride (SO₂F₂)

• Xian-Lin Chen and
• Hua-Li Qin

Beilstein J. Org. Chem. 2023, 19, 901–908, doi:10.3762/bjoc.19.68

• was not accomplished either by NMR analysis or chromatography. Conclusion In conclusion, we have developed an SO2F2-mediated ring-opening cross-coupling reaction of cyclobutanone oxime derivatives with alkenes for the synthesis of a class of novel elongated nitriles. The newly constructed δ-olefin

Pyridine C(sp²)–H bond functionalization under transition-metal and rare earth metal catalysis

• Haritha Sindhe,
• Malladi Mounika Reddy,
• Karthikeyan Rajkumar,
• Akshay Kamble,
• Amardeep Singh,
• Anand Kumar and
• Satyasheel Sharma

Beilstein J. Org. Chem. 2023, 19, 820–863, doi:10.3762/bjoc.19.62

• on subsequent deprotonation gives the branched alkylated product 4. Whereas, in case of styrene 3 a 1,2-insertion takes place possibly due to the formation of the stable benzallylic species 8, which on deprotonation gives the linear alkylated product 5. The C–H activation/C–C cross-coupling reaction

• , acrylates, allenes, and alkynes as coupling partners achieving the functionalized C(sp2)–H-olefinated pyridine frameworks via metal catalysis. ortho-C–H Alkenylation In 2012, Huang and co-workers [74] disclosed a ligand-free oxidative cross-coupling reaction of pyridine with acrylates, acrylamides, and

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

• -dimethyl-1,4-dihydroisoquinoline-3(2H)-one, 4-bromoisoquinoline-1,3(2H,4H)-dione and two α-bromo(phenyl)acetamides were examined under various conditions (base, solvent, thiophile, temperature) and structure/medium features that influence product distribution (Eschenmoser coupling reaction, Hantzsch

• thiazole synthesis and elimination to nitriles) were identified. The key factor that enables the successful Eschenmoser coupling reaction involves the optimum balance in acidity of nitrogen and carbon atoms of the intermediary α-thioiminium salts. Keywords: Eschenmoser coupling reaction; Hantzsch thiazole

• potential in the synthesis of various tyrosine kinase inhibitors, including hesperadin and the approved drug nintedanib. The key step of the synthesis involves the Eschenmoser coupling reaction (ECR) between a substituted 3-bromooxindole 1 and appropriate primary, secondary or tertiary thioamides which

Construction of hexabenzocoronene-based chiral nanographenes

• Ranran Li,
• Di Wang,
• Shengtao Li and
• Peng An

Beilstein J. Org. Chem. 2023, 19, 736–751, doi:10.3762/bjoc.19.54

• ]azepine and tetrabromothiophene-S,S-dioxide, followed by oxidative aromatization in the presence DDQ to afford compound 25 in an overall 75% yield. Suzuki−Miyaura cross-coupling reaction of compound 25 with (4-ethylphenyl)boronic acid in the presence of Pd(CH3CN)2Cl2, SPhos, and K3PO4 then furnished the

• the prefused building block in a 49% yield. Then naphthalene and phenanthrene residues were introduced into compound 33 through Suzuki coupling reaction, the corresponding precursors 34 and 36 were obtained respectively in high yields. The final cyclodehydrogenation using DDQ and TfOH proceeded

• Sonogashira cross-coupling reaction of phenylacetylene 50 and 1,4-dibromotetrafluorobenzene. The resulting bis[aryl(ethynyl)]tetrafluorobenzene 59 was able to undergo a 2-fold [4 + 2] cycloaddition reaction with cyclopentadienone 2, affording polyaromatic 60 in a 70% yield. The final step was the Scholl