Multicomponent reactions driving the discovery and optimization of agents targeting central nervous system pathologies

• Lucía Campos-Prieto,
• Aitor García-Rey,
• Eddy Sotelo and
• Ana Mallo-Abreu

Beilstein J. Org. Chem. 2024, 20, 3151–3173, doi:10.3762/bjoc.20.261

• /intramolecular Ullmann-type C–N coupling reactions. Azido-Ugi 4CR/cyclization (AU-4CR) strategy: The azido-Ugi four-component reaction (AU-4CR) is an elegant and atom economical approach for obtaining substituted tetrazoles, which are very relevant in medicinal chemistry [64]. When combined with suitable post

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

• )–H functionalization C–N coupling reaction by developing an electrochemical method for the bioconjugation of tyrosine in proteins/polypeptides with phenothiazine residues, achieving excellent site- and chemoselectivity (Scheme 4a). This method was inspired by an earlier work from the Gouin group

Catalysing (organo-)catalysis: Trends in the application of machine learning to enantioselective organocatalysis

• Stefan P. Schmid,
• Leon Schlosser,
• Frank Glorius and
• Kjell Jorner

Beilstein J. Org. Chem. 2024, 20, 2280–2304, doi:10.3762/bjoc.20.196

• physical organic chemistry with data-driven analysis techniques, in particular MLR, to gain a greater understanding of the enantioselectivity-determining steps for a C–N coupling catalysed by CPA derivatives (Figure 15A) [143]. Based on their findings that π–π interactions between the catalyst’s triazole

Novel oxidative routes to N-arylpyridoindazolium salts

• Oleg A. Levitskiy,
• Yuri K. Grishin and
• Tatiana V. Magdesieva

Beilstein J. Org. Chem. 2024, 20, 1906–1913, doi:10.3762/bjoc.20.166

• amount (5%) of the N,N’-diaryldihydrophenazine radical cation that is the byproduct corresponding to the intermolecular oxidative C–N coupling of the diarylamine A1 was detected in the reaction mixture. This emphasizes that the both processes are of the same nature and proceed through the same

• intermediate (i.e., the diarylamines’ radical cation) and indicates the dominance of the intramolecular cyclization over the intermolecular C–N coupling process. Oxidation of diarylamines in the presence of an excess of trifluoroacetic acid gave no targeted pyridoindazolium salts, whereas the amount of

Manganese-catalyzed C–C and C–N bond formation with alcohols via borrowing hydrogen or hydrogen auto-transfer

• Mohd Farhan Ansari,
• Atul Kumar Maurya,
• Abhishek Kumar and
• Saravanakumar Elangovan

Beilstein J. Org. Chem. 2024, 20, 1111–1166, doi:10.3762/bjoc.20.98

• team introduced a manganese(III) porphyrin system as a catalyst for the BH methodology to achieve C–N coupling reactions [43]. Various tertiary amines were isolated by coupling secondary amines and benzylic alcohols using Mn7 (3 mol %) in the presence of K2CO3 (20 mol %) under reflux conditions in

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

• complexes are important for the synthesis of heterocyclic and non-heterocyclic compounds. In 2009, Arthuis and co-workers developed a new process for the synthesis of 2-aroylindoles and 2-heteroaroylindoles by a one-pot palladium-catalyzed domino reaction that involves an initial C,N-coupling followed by

• making the process more environmentally friendly especially if we think about them in the industrial field. Clearly, the research in this field is ongoing and it will continue, and more active catalysts and new “green” synthetic approaches will be developed. Pd(0)-catalyzed domino C,N-coupling

Three-component N-alkenylation of azoles with alkynes and iodine(III) electrophile: synthesis of multisubstituted N-vinylazoles

• Jun Kikuchi,
• Roi Nakajima and
• Naohiko Yoshikai

Beilstein J. Org. Chem. 2024, 20, 891–897, doi:10.3762/bjoc.20.79

• motif in bioactive compounds and the synthetic utility of its olefinic C=C bond. The most extensively explored approach to this transformation is the transition metal-catalyzed C–N coupling between azoles and vinylating agents, including vinyl halides [4], boronates [5], sulfonium salts [6][7][8], and

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

• relevant heterocycles in high efficiency [10]. The Chan–Lam coupling is considered a greener alternative to traditional C–N coupling reactions, as it can be carried out under mild reaction conditions (room temperature and short reaction times, etc.), plus it does not require expensive metals like Pd, being

• driving forces for the development of the work discussed in this report. Results and Discussion Synthesis of o-(2-bromophenyl)aminoaniline via Buchwald–Hartwig C–N coupling One-pot synthesis of dibenzodiazepinones Our preliminary attempt to synthesize DBDAPs via B–H amination and carbonylation was carried

• the step-wise approach was 50% (Table 3). Synthesis of dibenzodiazepinones via Chan–Lam amination/carbonylative coupling Synthesis of o-(2-bromophenyl)aminoaniline via Chan–Lam C–N coupling Inspired by the previously independently reported work by Chan [24] and Lam [25] and co-workers, we considered

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

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

• the presence of N-(2-bromophenylthio)succinimide 1’ and copper catalyst led to intermolecular sulfenoamination of alkenes and subsequent C–N coupling to produce dihydrobenzothiazine structures 27 in a one-pot manner. Furthermore, deprotection of the amine unit by K2CO3 and Na metal was performed in

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

• benzyl radical on the O or N atom of the PINO radical, respectively. It should be noted that this method works well even without the excess of CH-reagent [94]. The formation of the mixture of C–O and C–N coupling products may be the main factor limiting the application of this method. The selective C–O

• substrates. DDQ is a popular mediator for oxidation reactions. It has been used for intramolecular dehydrogenative C–C bond formation between aromatic groups [127]. Using this method, the formation of polyaromatic systems was achieved in good yields (Scheme 26). The cross-dehydrogenative C–N coupling of

• benzyl iodides generated in situ. Electrolysis conditions: Constant current electrolysis until anodic potential 1.12 V vs Fc/Fc+, divided cell, reticulated vitreous carbon (RVC) anode(+). Electrochemical oxidative C–O/C–N coupling of alkylarenes with NHPI. Electrolysis conditions: Constant current

Dissecting Mechanochemistry III

• Lars Borchardt and
• José G. Hernández

Beilstein J. Org. Chem. 2022, 18, 1454–1456, doi:10.3762/bjoc.18.150

• intermolecular C–N coupling reactions using DDQ as an oxidant.

Mechanochemical halogenation of unsymmetrically substituted azobenzenes

• Dajana Barišić,
• Mario Pajić,
• Ivan Halasz,
• Darko Babić and
• Manda Ćurić

Beilstein J. Org. Chem. 2022, 18, 680–687, doi:10.3762/bjoc.18.69

• solvent-free synthesis of phenanthridinones via a cascaded oxidative C–N coupling followed by a halogenation reaction [50]. Only recently, our group carried out a detailed synthetic and mechanistic study of the mechanochemical PdII-catalyzed bromination of unsubstituted azobenzene (L1) by N

DDQ in mechanochemical C–N coupling reactions

• Shyamal Kanti Bera,
• Rosalin Bhanja and
• Prasenjit Mal

Beilstein J. Org. Chem. 2022, 18, 639–646, doi:10.3762/bjoc.18.64

• -Dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) is a commonly known oxidant. Herein, we report that DDQ can be used to synthesize 1,2-disubstituted benzimidazoles and quinazolin-4(3H)-ones via the intra- and intermolecular C–N coupling reaction under solvent-free mechanochemical (ball milling) conditions. In

• known, but limited reports are available for reactions carried out under solvent-free conditions [28][29]. However, improving environmentally benign methods [30][31] of C–N bond synthesis is of enormous significance [32][33][34]. In comparison to the metal-mediated C–N coupling reactions [35], the

• direct C–H amination is vital to provide many amine derivatives by sustainable methods [36][37]. The dehydrogenative C–N cross-coupling reactions from unreactive N–H and C–H bonds can lead to various nitrogen-containing heterocycles [32][38]. Herein, we disclose the DDQ-mediated oxidative C–N coupling

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

• alkyl halide to generate a copperII–nucleophile complex C and an alkyl radical. The formation of the R–Nu bond might occur through an in-cage pathway involving complex C (Scheme 20). In addition to carbazoles, the authors further described the C–N coupling of organic halides 45 with amides [83] and

• . Aerobic oxidative C(sp)–S coupling reaction. Copper-catalyzed alkylation of carbazoles with alkyl halides. C–N coupling of organic halides with amides and aliphatic amines. Copper-catalyzed C–X (N, S, O) bond formation reactions. Arylation of C(sp2)–H bonds of azoles. C–C cross-coupling of aryl halides

Effective microwave-assisted approach to 1,2,3-triazolobenzodiazepinones via tandem Ugi reaction/catalyst-free intramolecular azide–alkyne cycloaddition

• Maryna O. Mazur,
• Oleksii S. Zhelavskyi,
• Eugene M. Zviagin,
• Svitlana V. Shishkina,
• Vladimir I. Musatov,
• Maksim A. Kolosov,
• Elena H. Shvets,
• Anna Yu. Andryushchenko and
• Valentyn A. Chebanov

Beilstein J. Org. Chem. 2021, 17, 678–687, doi:10.3762/bjoc.17.57

• includes a [3 + 2] click reaction between the azide ion with the triple bond and further C–N coupling instead of the IAAC reaction. Compounds having no fused benzene ring or with a heterocyclic moiety instead could also be obtained via the tandem approach Ugi reaction/IAAC [15][16]. Despite the

Recent developments in enantioselective photocatalysis

• Callum Prentice,
• James Morrisson,
• Andrew D. Smith and
• Eli Zysman-Colman

Beilstein J. Org. Chem. 2020, 16, 2363–2441, doi:10.3762/bjoc.16.197

Chan–Evans–Lam N1-(het)arylation and N1-alkеnylation of 4-fluoroalkylpyrimidin-2(1H)-ones

• Viktor M. Tkachuk,
• Oleh O. Lukianov,
• Mykhailo V. Vovk,
• Isabelle Gillaizeau and
• Volodymyr A. Sukach

Beilstein J. Org. Chem. 2020, 16, 2304–2313, doi:10.3762/bjoc.16.191

• of being more available and stable [20][51][52]. A recently reported combined synthetic and spectroscopic study optimized the conditions for the C–N-coupling of NH compounds of various kinds (amines and NH-heterocycles) with boronic acid pinacol esters [20]. The use of acetonitrile as a solvent, with

Regiodivergent synthesis of functionalized pyrimidines and imidazoles through phenacyl azides in deep eutectic solvents

• Paola Vitale,
• Luciana Cicco,
• Ilaria Cellamare,
• Filippo M. Perna,
• Antonio Salomone and
• Vito Capriati

Beilstein J. Org. Chem. 2020, 16, 1915–1923, doi:10.3762/bjoc.16.158

• ], (c) carbon–sulfur bond-forming reactions [9], (d) directed ortho-metalation and nucleophilic acyl substitution strategies [10], (e) Pd-catalyzed aminocarbonylation of aryl iodides, Suzuki–Miyaura and Sonogashira cross-coupling reactions [11][12][13], (f) Cu-catalyzed C–N coupling reactions [14], and

When metal-catalyzed C–H functionalization meets visible-light photocatalysis

• Lucas Guillemard and
• Joanna Wencel-Delord

Beilstein J. Org. Chem. 2020, 16, 1754–1804, doi:10.3762/bjoc.16.147

• situ from molecular oxygen allowed the reoxidation of the Ru(II) active species for C–H activation. In 2015, Cho’s group became interested in implementing such mild and sustainable reoxidation protocol in a Pd-catalyzed C–H activation reaction, focusing mainly on an intramolecular direct C–N coupling

In silico rationalisation of selectivity and reactivity in Pd-catalysed C–H activation reactions

• Liwei Cao,
• Mikhail Kabeshov,
• Steven V. Ley and
• Alexei A. Lapkin

Beilstein J. Org. Chem. 2020, 16, 1465–1475, doi:10.3762/bjoc.16.122

• synthetic strategies. Such examples in recent years include olefin metathesis [1] as well as C–C and C–N coupling reactions [2], among the most obvious examples. While these reactions undoubtedly had very significant impacts on the development of much cleaner and efficient chemical synthesis strategies, the

Oxime radicals: generation, properties and application in organic synthesis

• Igor B. Krylov,
• Stanislav A. Paveliev,
• Alexander S. Budnikov and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2020, 16, 1234–1276, doi:10.3762/bjoc.16.107

• employing organolithium reagents are presented below (Scheme 14). The Grignard reagents demonstrated very similar results that are omitted. Among the major C–O coupling product (oxime ether 42) small amounts of C–N coupling products (nitrones 43) were detected in the case of sterically unhindered

Recent advances in photocatalyzed reactions using well-defined copper(I) complexes

• Mingbing Zhong,
• Xavier Pannecoucke,
• Philippe Jubault and
• Thomas Poisson

Beilstein J. Org. Chem. 2020, 16, 451–481, doi:10.3762/bjoc.16.42

• -photocatalyzed intramolecular decarboxylative C–N coupling of NHP esters using an in situ-formed heteroleptic copper complex (Scheme 23) [38]. This protocol, a versatile alternative to the Curtius rearrangement, was applied to a large variety of substrates, including primary/secondary alkyl, cycloalkyl, and

Palladium-catalyzed Sonogashira coupling reactions in γ-valerolactone-based ionic liquids

• László Orha,
• József M. Tukacs,
• László Kollár and
• László T. Mika

Beilstein J. Org. Chem. 2019, 15, 2907–2913, doi:10.3762/bjoc.15.284

• detected in imidazolium-type ILs. However, complete conversion of 1a was observed in [TBP][4EtOV], without Et3N, proving that the solvent can act as a base in itself (Table 1, #2) as it was demonstrated for Cu-catalyzed C–N coupling reactions [34]. When, we attempted to couple 1a and 2a in the absence of

Palladium-catalyzed synthesis and nucleotide pyrophosphatase inhibition of benzo[4,5]furo[3,2-b]indoles

• Hoang Huy Do,
• Saif Ullah,
• Alexander Villinger,
• Joanna Lecka,
• Jean Sévigny,
• Peter Ehlers,
• Jamshed Iqbal and
• Peter Langer

Beilstein J. Org. Chem. 2019, 15, 2830–2839, doi:10.3762/bjoc.15.276

• double C,N-coupling. All products are potent inhibitors of nucleotide pyrophosphatases with sensitivities and selectivities several times greater than those of previously reported inhibitors of h-NPP-1 and h-NPP-3 [37]. Biological activities of these compounds are prone to changes of the substituents

• extracted with dichloromethane. The organic layer was dried over Na2SO4, filtered and the solvent was evaporated in vacuo. The brown residue was purified by column chromatography (silica gel, heptane/ethyl acetate) to yield 3-bromo-2-(2-bromophenyl)benzofuran (3). General procedure for double C–N coupling