Cycloaddition reactions of heterocyclic azides with 2-cyanoacetamidines as a new route to C,N-diheteroarylcarbamidines

• Pavel S. Silaichev,
• Tetyana V. Beryozkina,
• Vsevolod V. Melekhin,
• Valeriy O. Filimonov,
• Andrey N. Maslivets,
• Vladimir G. Ilkin,
• Wim Dehaen and
• Vasiliy A. Bakulev

Beilstein J. Org. Chem. 2024, 20, 17–24, doi:10.3762/bjoc.20.3

• and Molecules, Department of Chemistry, KU Leuven, Celestijnenlaan 200F, B-3001 Leuven, Belgium 10.3762/bjoc.20.3 Abstract A novel and efficient base-catalyzed, transition-metal-free method for the synthesis of diheterocyclic compounds connected by an amidine linker, including apart from the common

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

• mechanistic aspects of the reaction and highlighted the potential of the NaI/PPh3 catalytic system for achieving efficient and transition-metal-free photocatalytic transformations. Following that, Li and his research group documented similar results (Scheme 4) [10]. They extensively investigated the

C–H bond functionalization: recent discoveries and future directions

• Indranil Chatterjee

Beilstein J. Org. Chem. 2023, 19, 1568–1569, doi:10.3762/bjoc.19.114

• its combination with organometallic chemistry for site-selective C−H bond functionalization [3][4]. Recent years have witnessed many viable strategies for the synthesis of complex targets utilizing photoredox catalysis, electroorganic catalysis, Lewis acid catalysis, and transition-metal-free

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

• Tzu-Yu Huang Mario Djugovski Sweta Adhikari Destinee L. Manning Sudeshna Roy Department of BioMolecular Sciences, School of Pharmacy, University of Mississippi, University, MS 38677, USA 10.3762/bjoc.19.111 Abstract Here, we report the first transition-metal-free defluorinative cycloaddition of

• organic azides in morpholine as a solvent forming C-4-morpholine functionalized fully decorated 1,2,3-triazoles with potential applications in pharmaceutical, biomedical, agrichemical, and materials sciences. This study fills a critical gap in the literature as it is a transition-metal-free and

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

• 102 were obtained in moderate to excellent yields with good to excellent enantioselectivities (Scheme 42) [76]. It should be noted that the authors did not define the exact role of the organocatalyst in the reaction mechanism. Transition-metal-free C–H sulfenylation of electron-rich arenes 103 by N

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

• elimination) more commonly associated with transition metal-mediated chemistry; however, halogen- or σ-hole bonding has recently emerged as a credible explanation for the diverse reactivity that iodonium ylides undergo. σ-Hole bonding theory offers a means to explain the occurrence of transition metal-free

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

Clauson–Kaas pyrrole synthesis using diverse catalysts: a transition from conventional to greener approach

• Dileep Kumar Singh and
• Rajesh Kumar

Beilstein J. Org. Chem. 2023, 19, 928–955, doi:10.3762/bjoc.19.71

• of N-arylpyrroles from various amines 78 via the reaction with 2,5-dimethoxytetrahydrofuran (2). Oxone is a mild, inexpensive, nontoxic, stable, and transition-metal-free catalyst that is very easy to handle during this transformation and provided high yields of the product. The authors also proposed

• (2). Further, a nucleophilic attack of amines 40 with intermediate A, MeOH removal, dehydration, and aromatization steps produce N-substituted pyrroles 41 in good to excellent yields. In 2019, Wani et al. [73] used the alkaline-earth metal-based catalyst Ca(NO3)2∙4H2O for a mild, transition metal

• -free and greener synthesis of various N-substituted pyrroles 43 under solvent-free conditions (Scheme 20a). For the optimizations of the reaction conditions, various catalysts (Ca(NO3)2∙4H2O, UO2(NO3)2∙6H2O, Bi(NO3)2∙5H2O) and solvents (H2O, CH3CN, EtOH, DMSO, DMF, MeOH, CH2Cl2, no solvent) were

NaI/PPh₃-catalyzed visible-light-mediated decarboxylative radical cascade cyclization of N-arylacrylamides for the efficient synthesis of quaternary oxindoles

• Dan Liu,
• Yue Zhao and
• Frederic W. Patureau

Beilstein J. Org. Chem. 2023, 19, 57–65, doi:10.3762/bjoc.19.5

• is mediated by visible light irradiation. A wide range of substrates bearing different substituents and derived from ubiquitous carboxylic acids, including α-amino acids, were synthesized and examined under this very mild, efficient, and cost effective transition-metal-free synthetic method. These

• limited substrate scopes (Scheme 1a). With the rapid development of sustainable chemistry, developing low-cost and transition-metal-free photocatalytic methods has become a strategic priority. In 2019 [54], the groups of Fu and Shang pioneered the photocatalytic decarboxylative alkylation of silyl enol

Functionalization of imidazole N-oxide: a recent discovery in organic transformations

• Koustav Singha,
• Imran Habib and
• Mossaraf Hossain

Beilstein J. Org. Chem. 2022, 18, 1575–1588, doi:10.3762/bjoc.18.168

• substitution reactions Metal-free coupling reaction through nucleophilic substitution of H-atom (SNH) In 2020, a C–H/C–Li coupling reaction between 2H-imidazole 1-oxides and pentafluorophenyllithium under transition metal-free conditions was reported by Timofey D. Moseev and co-workers [17]. The reaction

• provide the targeted products 11a–h. In the next year (2021), the same authors suggested another fascinating deoxygenative transition-metal-free SNH coupling reaction procedure of 2H-imidazole 1-oxides with polyphenols [10]. This process is convenient for producing bioactive bifunctional compounds

• . Transition-metal-free three-component reactions, cycloaddition reaction methodology and nucleophilic addition reaction, mainly these three types of reaction methodologies can be found in the literature reports. The approaches were greener and the reaction conditions were milder or not harsh in most of the

Derivatives of benzo-1,4-thiazine-3-carboxylic acid and the corresponding amino acid conjugates

• Péter Kisszékelyi,
• Tibor Peňaška,
• Klára Stankovianska,
• Mária Mečiarová and
• Radovan Šebesta

Beilstein J. Org. Chem. 2022, 18, 1195–1202, doi:10.3762/bjoc.18.124

• a reversible acidochromic behavior [30]. Zhao et al. demonstrated a three-component transition-metal-free aerobic method using a KI/DMSO/O2 system for the facile generation of iminobenzo-1,4-thiazines in moderate to good yield [31]. 3,4-Dihydro-2H-benzo-1,4-thiazine derivatives 6 were also

Tosylhydrazine-promoted self-conjugate reduction–Michael/aldol reaction of 3-phenacylideneoxindoles towards dispirocyclopentanebisoxindole derivatives

• Sayan Pramanik and
• Chhanda Mukhopadhyay

Beilstein J. Org. Chem. 2022, 18, 469–478, doi:10.3762/bjoc.18.49

• important functional group transformation for the synthesis of heterocyclic and carbocyclic building blocks and reactive intermediates. Besides the use of various reducing agents, it is observed that tosylhydrazine develops the transition-metal-free and highly chemoselective conjugate reduction of α,β

• dimerization produces dispirocyclopentanebisoxindoles in a transition-metal-free protocol (Scheme 1). Results and Discussion There is extensive application of 3-phenacylideneoxindoles generating diverse reaction strategies following the regioselective and diastereoselective synthesis of carbocyclic and

Regioselectivity of the S_EAr-based cyclizations and S_EAr-terminated annulations of 3,5-unsubstituted, 4-substituted indoles

• Jonali Das and
• Sajal Kumar Das

Beilstein J. Org. Chem. 2022, 18, 293–302, doi:10.3762/bjoc.18.33

• generated via 1,6-hydride shift in both I and II. Finally, an intramolecular Mannich-type cyclization then furnishes products 27. The cascade protocol enjoys several advantageous synthetic features, including high step- and atom-economy, transition-metal-free and room temperature conditions. In all cases

Transition-metal-free intramolecular Friedel–Crafts reaction by alkene activation: A method for the synthesis of some novel xanthene derivatives

• Tülay Yıldız,
• İrem Baştaş and
• Hatice Başpınar Küçük

Beilstein J. Org. Chem. 2021, 17, 2203–2208, doi:10.3762/bjoc.17.142

• conversions can occur. Conclusion In this study, a novel transition metal-free FCA method for the synthesis of 9-methyl-9-arylxanthenes has been developed. For this method, starting compounds with alkene structures suitable for our targets were synthesized. Among the synthesis methods of xanthene derivatives

Methodologies for the synthesis of quaternary carbon centers via hydroalkylation of unactivated olefins: twenty years of advances

• Thiago S. Silva and
• Fernando Coelho

Beilstein J. Org. Chem. 2021, 17, 1565–1590, doi:10.3762/bjoc.17.112

• radicals via hydrogen atom transfer reactions. In 2018, the Renaud group proposed an elegant solution to circumvent this problem by employing 4-tert-butylcatechol (TBC) as an external hydrogen atom source to regenerate the starting material under transition-metal-free conditions [118]. Employing α-EWG

Heterogeneous photocatalytic cyanomethylarylation of alkenes with acetonitrile: synthesis of diverse nitrogenous heterocyclic compounds

• Guanglong Pan,
• Qian Yang,
• Wentao Wang,
• Yurong Tang and
• Yunfei Cai

Beilstein J. Org. Chem. 2021, 17, 1171–1180, doi:10.3762/bjoc.17.89

• radical initiator under mild conditions. A wide range of structurally diverse nitrogenous heterocyclic compounds including indolines, oxindoles, isoquinolinones, and isoquinolinediones have been accessed in high yields. This heterogeneous protocol features base- and transition metal-free, good catalyst

• byproduct 15 after deprotonation. Conclusion We have demonstrated the application of a heterogeneous CN-K semiconducting photocatalyst in the cyanomethylarylation of alkenes with acetonitrile utilizing a readily available NHPI ester as radical initiator. This transition metal-free protocol tolerates a broad

Synthesis of β-triazolylenones via metal-free desulfonylative alkylation of N-tosyl-1,2,3-triazoles

• Soumyaranjan Pati,
• Renata G. Almeida,
• Eufrânio N. da Silva Júnior and
• Irishi N. N. Namboothiri

Beilstein J. Org. Chem. 2021, 17, 762–770, doi:10.3762/bjoc.17.66

• -triazoles with alkynes and Rh catalysed N1 and N2 selective alkylations [24][25]. As for metal-free approaches, besides synthesizing N-alkylated triazoles via 1,3-dipolar cycloaddition of alkyl azide with enols generated from carbonyl compounds under transition metal-free conditions [26], a direct

Metal-free visible-light-enabled vicinal trifluoromethyl dithiolation of unactivated alkenes

• Xiaojuan Li,
• Qiang Zhang,
• Weigang Zhang,
• Jinzhu Ma,
• Yi Wang and
• Yi Pan

Beilstein J. Org. Chem. 2021, 17, 551–557, doi:10.3762/bjoc.17.49

• successfully studied. However, the disproportionate dithiolation of alkenes is unknown. Herein, a transition-metal-free protocol is presented for the vicinal trifluoromethylthio–thiolation of unactivated alkenes via a radical process under mild conditions with a broad substrate scope and excellent tolerance

Deoxygenative C2-heteroarylation of quinoline N-oxides: facile access to α-triazolylquinolines

• Geetanjali S. Sontakke,
• Rahul K. Shukla and
• Chandra M. R. Volla

Beilstein J. Org. Chem. 2021, 17, 485–493, doi:10.3762/bjoc.17.42

• -aminoquinoline motif are shown in Figure 1 [46][47]. As a result, a variety of transition metal-catalyzed C2-selective aminations of azine N-oxides were explored extensively [28][29][30][31][32][33][34]. Additionally, various transition metal-free C2-aminations of these scaffolds were also investigated [35][36

1,2,3-Triazoles as leaving groups: S_NAr reactions of 2,6-bistriazolylpurines with O- and C-nucleophiles

• Dace Cīrule,
• Irina Novosjolova,
• Ērika Bizdēna and
• Māris Turks

Beilstein J. Org. Chem. 2021, 17, 410–419, doi:10.3762/bjoc.17.37

• ][45][46][47][48][49][50]. In the case of C-nucleophiles there are a few precedents of transition-metal-free substitution of chloro [51][52][53][54][55] or 1,2,4-triazolyl [56] moieties as leaving groups at the C6 position of purine. These transformations usually require prolonged time and elevated

• its HSQC spectrum, in which a cross peak clearly indicated the C(2’’)–H system. Conclusion The SNAr reactivity of 2,6-bis(1,2,3-triazol-1-yl)purine derivatives was extended with their substitution with O- and C-nucleophiles. The reactions proceeded under transition metal free conditions and revealed

Metal-free synthesis of biarenes via photoextrusion in di(tri)aryl phosphates

• Hisham Qrareya,
• Lorenzo Meazza,
• Stefano Protti and
• Maurizio Fagnoni

Beilstein J. Org. Chem. 2020, 16, 3008–3014, doi:10.3762/bjoc.16.250

• nowadays a growing interest in the forging of Ar–Ar bonds under transition-metal-free conditions [24][25]. Apart the most common pathways, e.g., the Friedel–Crafts functionalization [26] or nucleophilic aromatic substitution [27], alternative approaches have emerged that make use of photogenerated

Photosensitized direct C–H fluorination and trifluoromethylation in organic synthesis

• Shahboz Yakubov and
• Joshua P. Barham

Beilstein J. Org. Chem. 2020, 16, 2151–2192, doi:10.3762/bjoc.16.183

• catalysis and photochemistry. Where transition metal catalysis provides one strategy for C–H bond activation, transition-metal-free photochemical C–H fluorination can provide a complementary selectivity via a radical mechanism that proceeds under milder conditions than thermal radical activation methods

• visible-light-inactive molecules using PSCats 3.1 Benzylic C–H fluorination A seminal paper in the field of transition-metal-free direct C–H fluorination comes from Chen and co-workers, who applied aryl ketones as PSCats [135]. They discovered that the choice of the PS impacted the selective formation of

Metal-free synthesis of phosphinoylchroman-4-ones via a radical phosphinoylation–cyclization cascade mediated by K₂S₂O₈

• Qiang Liu,
• Weibang Lu,
• Guanqun Xie and
• Xiaoxia Wang

Beilstein J. Org. Chem. 2020, 16, 1974–1982, doi:10.3762/bjoc.16.164

• appropriate radical precursors through visible-light promoted systems [15][16], transition-metal-catalyzed systems [17][18], or transition-metal-free systems [19][20], have emerged as a powerful strategy for the synthesis of diversely functionalized chroman-4-one derivatives. Organophosphorus compounds are

• (DPPO) was not suitable for the transformation (Scheme 1b). So the development of metal-free and greener methods to approach chroman-4-ones bearing a phosphine oxide moiety is still highly desirable. Herein, we present a transition-metal-free radical cascade cyclization to access the desired chroman-4

Et₃N/DMSO-supported one-pot synthesis of highly fluorescent β-carboline-linked benzothiophenones via sulfur insertion and estimation of the photophysical properties

• Dharmender Singh,
• Vipin Kumar and
• Virender Singh

Beilstein J. Org. Chem. 2020, 16, 1740–1753, doi:10.3762/bjoc.16.146

• -metal-free strategy is presented to access novel β-carboline-tethered benzothiophenone derivatives from 1(3)-formyl-β-carbolines using elemental sulfur activated by Et3N/DMSO. This expeditious catalyst-free reaction proceeds through the formation of β-carboline-based 2-nitrochalcones followed by an

• Dharmender Singh Vipin Kumar Virender Singh Department of Chemistry, Dr. B R Ambedkar National Institute of Technology (NIT), Jalandhar, 144011, Punjab, India Department of Chemistry, Central University of Punjab, Bathinda, 151001, Punjab, India 10.3762/bjoc.16.146 Abstract A robust transition

Tuneable access to indole, indolone, and cinnoline derivatives from a common 1,4-diketone Michael acceptor

• Dalel El-Marrouki,
• Sabrina Touchet,
• Abderrahmen Abdelli,
• Hédi M’Rabet,
• Mohamed Lotfi Efrit and
• Philippe C. Gros

Beilstein J. Org. Chem. 2020, 16, 1722–1731, doi:10.3762/bjoc.16.144

• ; indoles 6, indolones 7, and cinnolines 8, starting from common substrates 1,4-diketones 5 and primary amines. The protocols developed here used mild conditions, were functional-group tolerant, transition-metal-free, proceeded in moderate to good yield, and could therefore easily be used in medicinal