Synthesis of highly substituted fluorenones via metal-free TBHP-promoted oxidative cyclization of 2-(aminomethyl)biphenyls. Application to the total synthesis of nobilone

• Ilya A. P. Jourjine,
• Lukas Zeisel,
• Jürgen Krauß and
• Franz Bracher

Beilstein J. Org. Chem. 2021, 17, 2668–2679, doi:10.3762/bjoc.17.181

• group (Scheme 2) [33]. In contrast to transition-metal-mediated approaches [27], metal-free oxidative methods are attractive not only from an ecological point of view, but also due to the typically low cost of the applied oxidants. Biarylcarboxaldehydes were cyclized to fluorenones using K2S2O8 [34

• cyclic lactones [69]. The intramolecular cyclization of the acyl radical A gives the tricyclic radical species C, which then forms fluorenone (3) after abstraction of a hydrogen radical by an additional equivalent of the tert-butoxy radical. Conclusion In summary, we have demonstrated that the metal-free

Recent advances in organocatalytic asymmetric aza-Michael reactions of amines and amides

• Pratibha Sharma,
• Raakhi Gupta and
• Raj K. Bansal

Beilstein J. Org. Chem. 2021, 17, 2585–2610, doi:10.3762/bjoc.17.173

• metal-free small organic molecules as catalysts has been a landmark advancement in organic synthesis in the recent past [16]. MacMillan and co-workers for the first time in the year 2000 termed these catalysts as ‘Organocatalysts’ [17]. It was followed by intense activity and phenomenal rise in the

Synthesis of phenanthridines via a novel photochemically-mediated cyclization and application to the synthesis of triphaeridine

• Songeziwe Ntsimango,
• Kennedy J. Ngwira,
• Moira L. Bode and
• Charles B. de Koning

Beilstein J. Org. Chem. 2021, 17, 2340–2347, doi:10.3762/bjoc.17.152

• , such as ionic liquid- and transition metal-catalyzed and other metal-free transformations [1]. A strategically diverse route to phenanthridines involves intramolecular cyclization of biaryl oximes, allowing for the formation of a new C–N bond. Such a strategy was explored by Deb and Yoshikai in the Fe

A visible-light-induced, metal-free bis-arylation of 2,5-dichlorobenzoquinone

• Pieterjan Winant and
• Wim Dehaen

Beilstein J. Org. Chem. 2021, 17, 2315–2320, doi:10.3762/bjoc.17.149

• Pieterjan Winant Wim Dehaen Molecular Design and Synthesis, Department of Chemistry, KU Leuven, Celestijnenlaan 200F, 3001 Leuven, Belgium 10.3762/bjoc.17.149 Abstract A metal-free protocol for the direct bis-arylation of 2,5-dichlorobenzoquinone with aryldiazonium salts is reported. The reactive

• issues [38][39]. Since bis-arylated quinones are promising substrates in a range of different applications (vide infra), a simple and effective method of synthesizing these types of compounds would be of great use. Motivated by the results of König et al., we set out to develop a metal-free strategy

• developed a straightforward metal-free procedure for the synthesis of bis-arylated 2,5-dichlorobenzoquinones. The reaction is tolerant towards a wide range of functional groups, occurs under mild conditions in an environmentally benign solvent and does not require further purification of the reaction

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

• ]. Therefore, there has been an increase in arylation methods using Friedel–Crafts alkylation (FCA) protocols without transition metals [35][36]. Environmentally friendly methods, in which metal-free catalysts are used, have come to the fore and are gaining importance because there are many disadvantages of

• 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

Chemical syntheses and salient features of azulene-containing homo- and copolymers

• Vijayendra S. Shetti

Beilstein J. Org. Chem. 2021, 17, 2164–2185, doi:10.3762/bjoc.17.139

• and larger cathodic shift of the oxidation potential in these polymers compared to their metal-free counterparts. In 2012, Hawker and co-workers [22], along with 17–20, also synthesized a polymer 45 which had azulene and thiophene units connected via the 4,7-positions of azulene. The reaction of 4,7

Cerium-photocatalyzed aerobic oxidation of benzylic alcohols to aldehydes and ketones

• Girish Suresh Yedase,
• Sumit Kumar,
• Jessica Stahl,
• Burkhard König and
• Veera Reddy Yatham

Beilstein J. Org. Chem. 2021, 17, 1727–1732, doi:10.3762/bjoc.17.121

• thermal conditions. Significant advances were made for the oxidation of benzylic alcohols by using metal-based photocatalysts [38][39][40][41][42][43][44][45][46] and metal-free photocatalysis [47][48][49][50][51][52][53] in combination with various oxidants, such as TBHP and DDQ [54][55]. However, the

A recent overview on the synthesis of 1,4,5-trisubstituted 1,2,3-triazoles

• Pezhman Shiri,
• Ali Mohammad Amani and
• Thomas Mayer-Gall

Beilstein J. Org. Chem. 2021, 17, 1600–1628, doi:10.3762/bjoc.17.114

• preparation of 1,4,5-trisubstituted 1,2,3-triazoles have gained much attention in triazole chemistry. Generally, two protocols for the synthesis of this type of triazole derivatives could be mentioned (metal or metal-free catalysis). Contrary to sporadic attempts [34], there is no detailed, systematic, and

• current review considers the synthesis of diverse 1,4,5-trisubstituted 1,2,3-triazoles via metal- and metal-free catalytic routes. Synthesis and mechanism aspects of this category of fully functionalized triazoles are reported in detail in the current review article. We believe a precise and systematic

• procedures for the efficient preparation of these significant products is highly required. Review Metal-free synthesis of fully decorated triazoles Developing metal-free protocols for the synthesis of triazole derivatives has been considered as growingly attractive yet challenging objectives in the

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

Synthesis of 1-indolyl-3,5,8-substituted γ-carbolines: one-pot solvent-free protocol and biological evaluation

• Premansh Dudhe,
• Mena Asha Krishnan,
• Kratika Yadav,
• Diptendu Roy,
• Krishnan Venkatasubbaiah,
• Biswarup Pathak and
• Venkatesh Chelvam

Beilstein J. Org. Chem. 2021, 17, 1453–1463, doi:10.3762/bjoc.17.101

• the literature, there is only a limited number of direct synthetic procedures to prepare γ-carbolines till date [28], and this gives a cutting edge advantage to our new protocol wherein a solvent and metal-free direct access to the γ-carboline core from substituted indole-2-aldehyes and glycine ester

Icilio Guareschi and his amazing “1897 reaction”

• Gian Cesare Tron,
• Alberto Minassi,
• Giovanni Sorba,
• Mara Fausone and
• Giovanni Appendino

Beilstein J. Org. Chem. 2021, 17, 1335–1351, doi:10.3762/bjoc.17.93

• “Guareschi 1897 reaction”, is one of the most unusual reactions in organic chemistry, involving the radical-mediated paradoxical aerobic generation of hydrocarbons in near-neutral water solution. A discussion of the mechanism of this amazing reaction, the only metal-free process that generates hydrocarbons

Photoinduced post-modification of graphitic carbon nitride-embedded hydrogels: synthesis of 'hydrophobic hydrogels' and pore substructuring

• Cansu Esen and
• Baris Kumru

Beilstein J. Org. Chem. 2021, 17, 1323–1334, doi:10.3762/bjoc.17.92

• novelty. Here, a metal-free semiconductor graphitic carbon nitride (g-CN)-embedded hydrogel as an initial network was synthesized via redox-couple initiation under dark conditions. Post-photomodification of so-formed hydrogel, thanks to the photoactivity of the embedded g-CN nanosheets, was exemplified in

• -sustainable semiconductors are slowly being replaced by a new generation of semiconductors. Graphitic carbon nitride (g-CN) is a metal-free polymeric semiconductor that is mainly composed of carbon and nitrogen elements by tri-s-triazine, triazine imide, or heptazine repeating units [16][17][18]. g-CN

A comprehensive review of flow chemistry techniques tailored to the flavours and fragrances industries

• Guido Gambacorta,
• James S. Sharley and
• Ian R. Baxendale

Beilstein J. Org. Chem. 2021, 17, 1181–1312, doi:10.3762/bjoc.17.90

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

Recent advances in palladium-catalysed asymmetric 1,4–additions of arylboronic acids to conjugated enones and chromones

• Jan Bartáček,
• Jan Svoboda,
• Martin Kocúrik,
• Jaroslav Pochobradský,
• Alexander Čegan,
• Miloš Sedlák and
• Jiří Váňa

Beilstein J. Org. Chem. 2021, 17, 1048–1085, doi:10.3762/bjoc.17.84

• ]. Evaluation of current state and outlook Asymmetric addition reactions to enones have so far been described in the literature in connection with catalysis. The catalyst is usually a complex of a transition metal with a suitable ligand. However, metal-free catalysis is also known [64]. Among the most

Application of the Meerwein reaction of 1,4-benzoquinone to a metal-free synthesis of benzofuropyridine analogues

• Rashmi Singh,
• Tomas Horsten,
• Rashmi Prakash,
• Swapan Dey and
• Wim Dehaen

Beilstein J. Org. Chem. 2021, 17, 977–982, doi:10.3762/bjoc.17.79

• . Electrophilic substitution and further condensations give polycyclic systems, including oxazolo- and chromeno-fused analogues. Keywords: benzofuropyridines; benzoquinones; dibenzofurans; Meerwein reaction; metal-free synthesis; Introduction Dibenzofurans are important oxygen-containing heterocycles present in

• work focuses on a metal-free approach for the synthesis of benzofuropyridine analogues. Results and Discussion The synthesis of target compound 13 involved three steps (Scheme 1). C–H Arylation, as needed in the first step, is usually carried out using transition metal catalysis [31]. Furthermore

• we plan to expand this chemistry and carry out a bioactivity study in due course. Biologically relevant 2-oxydibenzofuran-containing structures 1–6. Representative bioactive structures containing benzofuro-fused pyridine analogues 7–9. Strategy for metal-free access to benzofuropyridine 13

Metal-free glycosylation with glycosyl fluorides in liquid SO₂

• Krista Gulbe,
• Jevgeņija Lugiņina,
• Edijs Jansons,
• Artis Kinens and
• Māris Turks

Beilstein J. Org. Chem. 2021, 17, 964–976, doi:10.3762/bjoc.17.78

• equilibrium. Keywords: fluorosulfite; glycosyl fluoride; Lewis acid; liquid sulfur dioxide; metal-free glycosylation; Introduction The glycosylation reaction is still one of the most important and basic synthetic strategies in carbohydrate chemistry that provides access to the various types of

• not possess the participating group at C2 position, still react through the oxocarbenium ion intermediate. Conclusion In summary, novel sulfur dioxide-assisted and metal-free glycosylation conditions by employing a combination of glycosyl fluoride as the glycosyl donor and liquid SO2 as both solvent

Highly regio- and stereoselective phosphinylphosphination of terminal alkynes with tetraphenyldiphosphine monoxide under radical conditions

• Dat Phuc Tran,
• Yuki Sato,
• Yuki Yamamoto,
• Shin-ichi Kawaguchi,
• Shintaro Kodama,
• Akihiro Nomoto and
• Akiya Ogawa

Beilstein J. Org. Chem. 2021, 17, 866–872, doi:10.3762/bjoc.17.72

• derivatives having various substituents on the ethylene moiety. In particular, synthetic methods that do not use metal catalysts and reagents are expected to be very effective in manufacturing precision materials and pharmaceuticals [32][33][34][35][36][37]. To develop metal-free methods for the synthesis of

Microwave-assisted multicomponent reactions in heterocyclic chemistry and mechanistic aspects

• Shivani Gulati,
• Stephy Elza John and
• Nagula Shankaraiah

Beilstein J. Org. Chem. 2021, 17, 819–865, doi:10.3762/bjoc.17.71

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

• , MG, Brazil 10.3762/bjoc.17.66 Abstract Desulfonylative alkylation of N-tosyl-1,2,3-triazoles under metal-free conditions leading to β-triazolylenones is reported here. The present study encompasses the synthesis of triazoles with a new substitution pattern in a single step from cyclic 1,3-dicarbonyl

• -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

• functionalization of triazoles under metal-free conditions has been reported. These include the Broensted acid-catalysed N2 alkylation [27], organocatalytic N1 alkylation [28][29], N2-arylation using hypervalent iodine (Scheme 1c) [30], N2-alkylation involving radical intermediate [31], pyridine-N-oxide-mediated N1

Valorisation of plastic waste via metal-catalysed depolymerisation

• Francesca Liguori,
• Carmen Moreno-Marrodán and
• Pierluigi Barbaro

Beilstein J. Org. Chem. 2021, 17, 589–621, doi:10.3762/bjoc.17.53

• described in detail. Solvolytic depolymerisations can also be promoted by metal-free soluble acid or base catalysts. However, concentrated solutions, quasistoichiometric amounts or strong mineral acids (HNO3, H2SO4, H3PO4) or bases (NaOH, KOH, potassium butoxide) are often required, particularly for

• [ZnCl3] (bmim = 1-butyl-3-methylimidazolium, Table 4, entry 2) [228] were recently studied, showing higher catalytic activity compared to metal-free ionic liquids (i.e., bmim chloride), the conventional catalysts (i.e., ZnCl2, Zn(OAc)2) or the analogous Mn, Co and Cu ionic liquids. Typically, 80–85% BHET

• 3) [229]. Based on infrared studies, the higher catalytic activities of the metallated ILs was attributed to their higher Lewis acidity compared to both the metal-free catalysts and the metal salts. A mechanism was therefore proposed in which a synergistic effect of the metallated ILs takes place

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

• . Keywords: alkenes; difunctionalization; metal-free; photoredox; trifluoromethylthiolation; Introduction The incorporation of fluorine atoms into drug molecules will significantly enhance the physical, chemical, and biological properties of the pharmaceuticals [1][2][3][4][5][6]. Modifying drug candidates

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

• to amination and amidation, there are few reports on metal-free C2-heteroarylation of pyridine N-oxides. In 1984, Rogers demonstrated the synthesis of 2-triazolylpyridines from 2-azidopyridines and phenylacetylene [51]. Along the same lines, Keith reported methodologies for the C2-imidazolylation and

• derivatives, we performed a sequential one-pot synthesis by combining a Cu(I)-catalyzed “Click” reaction of phenylacetylene (7) with TsN3 and a metal-free C2-heteroarylation of quinoline N-oxide (1a, Scheme 6b). Remarkably, the yield of the desired product 3a in the one-pot synthesis (80%) was comparable to

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

CF₃-substituted carbocations: underexploited intermediates with great potential in modern synthetic chemistry

• Anthony J. Fernandes,
• Armen Panossian,
• Bastien Michelet,
• Agnès Martin-Mingot,
• Frédéric R. Leroux and
• Sébastien Thibaudeau

Beilstein J. Org. Chem. 2021, 17, 343–378, doi:10.3762/bjoc.17.32