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

• irrespective of the nature and position of the substituent [39]. The supposed reaction mechanism for the reaction is shown in Scheme 3. Initially, the presence of bromine as an electron-withdrawing substituent lowers the LUMO energy to facilitate the cycloaddition process of acrolein with organic azide. The

• corresponding triazole products in moderate yield (Scheme 8) [42]. The authors proposed a reaction mechanism in which the β-thioenaminone 18 tolerates deprotonation to afford anionic intermediate 21 through the tautomer 20 in the presence of a base. In the next step, the nucleophilic addition of 21 to the azide

• -membered sulfur-containing cycle (Scheme 23) [52]. Some reactions were performed to screen the reaction mechanism in detail. To find out if the reaction proceeds through a radical pathway, tetramethylpiperidine-1-oxyl (TEMPO) was added to the reaction. The corresponding product was obtained in high yield

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

Iodine-catalyzed electrophilic substitution of indoles: Synthesis of (un)symmetrical diindolylmethanes with a quaternary carbon center

• Thanigaimalai Pillaiyar,
• Masoud Sedaghati,
• Andhika B. Mahardhika,
• Lukas L. Wendt and
• Christa E. Müller

Beilstein J. Org. Chem. 2021, 17, 1464–1475, doi:10.3762/bjoc.17.102

• . This class of compounds also possesses potential for the development of CB2-selective or dual CB1/CB2-receptor antagonists. Based on previous reports [25][26][27][28][29][30][31][32][33][34][35][43][44][45][46][47][48][49][50][51][52][53], a plausible reaction mechanism is proposed for the synthesis of

• and 3ad. Plausible reaction mechanism for the synthesis of fluoromethylated unsymmetrical DIMs, shown for compound 3a as an example. Optimization of the reaction conditions for the preparation of 5-methoxy-3-(2,2,2-trifluoro-1-(1H-indol-3-yl)-1-phenylethyl)-1H-indole (3a)a. Substrate scope of the

Fritsch–Buttenberg–Wiechell rearrangement of magnesium alkylidene carbenoids leading to the formation of alkynes

• Tsutomu Kimura,
• Koto Sekiguchi,
• Akane Ando and
• Aki Imafuji

Beilstein J. Org. Chem. 2021, 17, 1352–1359, doi:10.3762/bjoc.17.94

• of 2-monoaryl-substituted sulfoxide 2g in good yields (Table 2, entries 9 and 10). Reaction mechanism The substrate scope results suggest that aryl and alkynyl groups are migratable, whereas alkyl groups are not. The FBW rearrangement of magnesium alkylidene carbenoids seems to be an anionotropic

• reactivity between geometric isomers, the formation of alkynes via the 1,2-rearrangement of free alkylidene carbenes is unlikely. To gain insight into the reaction mechanism, 13C-labeled sulfoxides [13C]-(E)-2e and [13C]-(Z)-2e were prepared from acetophenone-α-13C and HWE reagent (Scheme 6a), and each

• and that the C–Me bond was maintained during the reaction. Based on these results, we propose the reaction mechanism as outlined in Scheme 7. When substituent R1 with a high migratory aptitude, such as an aryl group and alkynyl group, is located trans to the chloro group, the 1,2-rearrangement

N-tert-Butanesulfinyl imines in the asymmetric synthesis of nitrogen-containing heterocycles

• Joseane A. Mendes,
• Paulo R. R. Costa,
• Miguel Yus,
• Francisco Foubelo and
• Camilla D. Buarque

Beilstein J. Org. Chem. 2021, 17, 1096–1140, doi:10.3762/bjoc.17.86

• %) from allylic sulfonamides 40 and Togni’s reagent (41). The reaction mechanism is proposed based on DFT calculations. In this study, they observed an intramolecularly intermediate Cu(III) species, and the sulfinamide acts as a direction group and nucleophile [75] (Scheme 14). Asymmetric synthesis of

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

• can be performed in widely available glass pressure tubes. Detection of the FSO2− species by 19F NMR (471 MHz, D2O). Computational study of reaction mechanism α-11 + MeOH → α-13c in the presence of and in absence of SO2 (Gaussian 09, Revision D.01; Gaussian, Inc.; m052x method and the 6-31+g(d) basis

Manganese/bipyridine-catalyzed non-directed C(sp³)–H bromination using NBS and TMSN₃

• Kumar Sneh,
• Takeru Torigoe and
• Yoichiro Kuninobu

Beilstein J. Org. Chem. 2021, 17, 885–890, doi:10.3762/bjoc.17.74

• (sp3)–H bromination reaction. The proposed reaction mechanism is shown in Scheme 5, which involves the following steps. (1) The reaction between NBS and TMSN3 generates bromine azide via the elimination of N-(trimethylsilyl)succinimide [52][53]; (2) bromine and azide radicals are then formed via

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

Synthetic reactions driven by electron-donor–acceptor (EDA) complexes

• Zhonglie Yang,
• Yutong Liu,
• Kun Cao,
• Xiaobin Zhang,
• Hezhong Jiang and
• Jiahong Li

Beilstein J. Org. Chem. 2021, 17, 771–799, doi:10.3762/bjoc.17.67

• reaction mechanism for this transformation is as follows (Scheme 6): Firstly, O-aryloxime 11 forms EDA complex 13 by action of DABCO·(SO2)2 and then undergoes light-promoted single-electron transfer, affording the 2,4-dinitrophenol anion, nitrogen radical 14, and radical 15, respectively. 1,5-HAT (hydrogen

• step without any transition-metal catalyst, ligand, or photocatalyst, this method possesses a splendid application prospect. The reaction mechanism is as follows (Scheme 48): Firstly, carbon disulfide combines with N-methylaniline (134) in the presence of Cs2CO3 to form thiolate 136. Thiolate 136 is

• including EPR, NMR, and DFT have been carried out to prove that the reaction mechanism is consistent with inference (Scheme 58). The construction of C–O bonds and C–H bonds Although there have been few cases of constructing C–O bonds and C–H bonds via EDA-complex pathways in recent years, we also summarized

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

• reaction mechanism, the crude reaction mixture of 1a with 2b after 10 h was analysed by NMR which suggested the formation of C-tosyl intermediate 4b' besides the expected product 3e (Scheme 3b). The two compounds were later purified and characterized. Subsequently, the cyclopentan-1,3-dione derived O-tosyl

Synthesis of dibenzosuberenone-based novel polycyclic π-conjugated dihydropyridazines, pyridazines and pyrroles

• Ramazan Koçak and
• Arif Daştan

Beilstein J. Org. Chem. 2021, 17, 719–729, doi:10.3762/bjoc.17.61

• –Alder reactions, depending on the structure of the diene and the reaction conditions [64]. A proposed reaction mechanism for the formation of the dibenzosuberenone derivatives 3 and 4 is illustrated in Scheme 3. Although 3k was isolated, 3l could not be detected in the reaction mixture due to its

• dibenzosuberenone (1) with tetrazines 2a–l. Inverse electron-demand Diels–Alder reactions between dibenzosuberenone 1 and tetrazines 2ka and 2lb. a5.55 mmol 1, 3.70 mmol 2k, 10 mL toluene, 120 ˚C, 48 h. b4.85 mmol 1, 0.98 mmol 2l, 100 ˚C, overnight (solvent free). Proposed reaction mechanism for the formation of

[2 + 1] Cycloaddition reactions of fullerene C₆₀ based on diazo compounds

• Yuliya N. Biglova

Beilstein J. Org. Chem. 2021, 17, 630–670, doi:10.3762/bjoc.17.55

• methanofullerenes via tosyl derivatives. (BtOH is 1H-benzotriazol-1-ol.) The synthetic route to [60]PCBM via tosylhydrazine. The reaction mechanism of fullerene cyclopropanation via tosylhydrazine derivatives. Serial synthesis of [6,6]-phenyl-C61-butyric acid esters 87–91 [114], 92–96 [113][115], and 97 [116

• . Polysubstituted diphenylmethanofullerenes 169–177. Fullerene-containing phenylacetylene dendrimers of the 1st and 2nd generation. Dibenzosuberane-substituted fullerene derivatives 196 and 197. Methods for the synthesis of methanofullerenes C60. Synthesis of diphenyl-substituted fulleroids 1 and 2. The reaction

• mechanism of a family of fulleroids by cyclopropanation of C60 with diazo compounds. Synthesis of 1,2-methanobuckminsterfullerene 3 and related fulleroid 4. Synthesis of dimethylmethanofullerene 6 from dimethyldiazomethane via the formation of annulene 5. ODCB = orthodichlorobenzene. Synthesis of

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

• and a 20:1 excess of strong base potassium tert-butoxide as cocatalyst (Table 1, entry 1) [183]. Although the reaction mechanism was not investigated in detail, it was suggested that cleavage of the ester linkage may occur in a concerted manner through the reported heterolytic route [184][185]. The

• ) [191]. No hypotheses for the reaction mechanism were formulated. Higher conversion (64%) and selectivity (99%) were observed using the bulkier xylyl derivative Ru(triphos-xyl)tmm (Table 1, entry 4), which was attributed to reduced catalyst degradation [192]. The catalyst could be employed for the

• electronic effect of the ligand [267]. A reaction mechanism for PLA depolymerisation was proposed, consisting of two consecutive first-order steps, in which Me-La production follows the formation of chain-end groups intermediates [265]. A zinc–N-heterocyclic carbene complex was used as catalysts for the

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

• corresponding SCF3 adducts. In addition, boldenone- and ᴅ-glucose-derived terminal alkenes were compatible with the conditions affording the corresponding products 5l and 5m in moderate to good yields. To gain insight into the reaction mechanism, control experiments were conducted under the standard conditions

The synthesis of chiral β-naphthyl-β-sulfanyl ketones via enantioselective sulfa-Michael reaction in the presence of a bifunctional cinchona/sulfonamide organocatalyst

• Deniz Tözendemir and
• Cihangir Tanyeli

Beilstein J. Org. Chem. 2021, 17, 494–503, doi:10.3762/bjoc.17.43

• the product 12a with a final ee of 62% (Table 2, entry 18). This unexpected phenomenon could be linked to an enthalpic factor that favors the formation of the major enantiomer at higher temperature, or due to a change in the reaction mechanism when the temperature was altered. The most enantioenriched

Synthetic strategies of phosphonodepsipeptides

• Jiaxi Xu

Beilstein J. Org. Chem. 2021, 17, 461–484, doi:10.3762/bjoc.17.41

• compared with alternative coupling reagents. Various optically active phosphonodepsidipeptides 113–118 were synthesized. The reaction mechanism was further studied, revealing that the reaction proceeds through benzotriazolyl esters as was shown by the comparison with other coupling reagents, including DCC

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

Selective synthesis of α-organylthio esters and α-organylthio ketones from β-keto esters and sodium S-organyl sulfurothioates under basic conditions

• Jean C. Kazmierczak,
• Roberta Cargnelutti,
• Thiago Barcellos,
• Claudio C. Silveira and
• Ricardo F. Schumacher

Beilstein J. Org. Chem. 2021, 17, 234–244, doi:10.3762/bjoc.17.24

• between the keto and the enol tautomer is given based on the 1H NMR analysis. These results are consistent with the report by Tan and collaborators [55] and are evidence to help understand the reaction mechanism. Although detailed mechanisms for these reactions remain to be elucidated, the literature has

Direct synthesis of anomeric tetrazolyl iminosugars from sugar-derived lactams

• Michał M. Więcław and
• Bartłomiej Furman

Beilstein J. Org. Chem. 2021, 17, 115–123, doi:10.3762/bjoc.17.12

• azide addition to nitriles [45]. It is important to note that the computational investigation of this reaction mechanism was not a primary goal of this work. That said, we consider this simple, crude DFT research to support our model of the transformation described herein. Conclusion During the course

• requires protic conditions, in opposition to what is generally agreed upon for these type of reactions. An alternative reaction mechanism is proposed and provisionally confirmed with DFT calculations. Moreover, selected α-tetrazolyl-iminosugars were subjected to further transformations, yielding new

• the nucleophile attack according to Woerpel’s model [24]. Proposed reaction mechanism for the described Ugi–azide reaction variant. Possible pathway for spontaneous imine formation. Values reported are in kcal·mol−1. A possible path for tetrazole formation in the described conditions. Values reported

Synthesis of aryl 2-bromo-2-chloro-1,1-difluoroethyl ethers through the base-mediated reaction between phenols and halothane

• Yukiko Karuo,
• Ayaka Kametani,
• Atsushi Tarui,
• Kazuyuki Sato,
• Kentaro Kawai and
• Masaaki Omote

Beilstein J. Org. Chem. 2021, 17, 89–96, doi:10.3762/bjoc.17.9

• functionalized aryl 2-bromo-2-chloro-1,1-difluoroethyl ethers as well as several considerations of the reaction mechanism. Results and Discussion We began our study to optimize the reaction conditions (Table 1). When two equivalents of halothane and sodium hydride (NaH) were treated with phenol (1a) at room

• reaction mechanism as shown in Scheme 4a. The reaction was carried out in a stepwise procedure in which the phenoxide was prepared by mixing equimolar amounts of phenol (1a) and NaH to consume all NaH in the reaction mixture, and then halothane was added to the reaction mixture. The stepwise reaction gave

• previous work reported by Yagupol’skii et al. Intramolecular 1,4-addition of 2o. Proposed reaction mechanism. Optimization of the reaction conditions with phenol (1a). The reaction scope with various phenols. Supporting Information Supporting Information File 184: Characterization data for 2b–p and copies

Silver-catalyzed synthesis of β-fluorovinylphosphonates by phosphonofluorination of aromatic alkynes

• Yajing Zhang,
• Qingshan Tian,
• Guozhu Zhang and
• Dayong Zhang

Beilstein J. Org. Chem. 2020, 16, 3086–3092, doi:10.3762/bjoc.16.258

• extremely low yield. Another H-phosphonate, namely dimethyl phosphite, was a suitable substrate for this transformation and provided the products 3 in good yield (Scheme 3). The well-known radical-trapping reagent 2,2,6,6-tetramethylpiperidine-N-oxyl (TEMPO) was used to gain an insight into the reaction

• mechanism. As illustrated in Scheme 4, the addition of 1 equiv TEMPO suppressed the reaction. In addition, 4-ethynylaniline (1f) reacted with Selectfluor® and dimethyl phosphite under the optimized conditions to afford the expected product in 13% yield, and no competitive electrophilic compound 4f was

Deoxyfluorination of acyl fluorides to trifluoromethyl compounds by FLUOLEAD^®/Olah’s reagent under solvent-free conditions

• Yumeng Liang,
• Akihito Taya,
• Zhengyu Zhao,
• Norimichi Saito and
• Norio Shibata

Beilstein J. Org. Chem. 2020, 16, 3052–3058, doi:10.3762/bjoc.16.254

• trifluoromethyl compounds under the same reaction conditions. A reaction mechanism is proposed. Keywords: acyl fluorides; deoxyfluorination; fluorine; solvent-free; trifluoromethyl group; Introduction Due to an impressively wide effect of fluorine on the biological activity, the insertion of fluorine atoms or

All-carbon [3 + 2] cycloaddition in natural product synthesis

• Zhuo Wang and
• Junyang Liu

Beilstein J. Org. Chem. 2020, 16, 3015–3031, doi:10.3762/bjoc.16.251

• -unsaturated enone to afford conidiogenone B (171) in 32% yield upon treatment with RhCl3 in microwave. The reaction mechanism of Danheiser’s [3 + 2] annulation is shown according to the Danheiser’s proposal [74] (Scheme 13C, inset). Initial complexation of the α,β-unsaturated ketone 167 and titanium

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

• strong electron-donating substituents, especially when present in the para-position (see the case of 4a–c). Unfortunately, the unsymmetric biaryl 4e was detected in a very poor amount. To investigate the reaction mechanism, some photophysical parameters of compounds 1 and 3 were determined. All the

Three-component reactions of aromatic amines, 1,3-dicarbonyl compounds, and α-bromoacetaldehyde acetal to access N-(hetero)aryl-4,5-unsubstituted pyrroles

• Wenbo Huang,
• Kaimei Wang,
• Ping Liu,
• Minghao Li,
• Shaoyong Ke and
• Yanlong Gu

Beilstein J. Org. Chem. 2020, 16, 2920–2928, doi:10.3762/bjoc.16.241

• , affording the polysubstituted pyrazolo[3,4-b]pyridine 5a in 53% yield. The formation of an imine intermediate V may be involved in the reaction mechanism, and the enamine form of V contained two nucleophilic sites to react with a molecule of 3a, which generated the intermediate VI. Finally, VI underwent an