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

• regioselective in forming 16, which is a valuable building block for various condensation reactions to yield a diverse set of products, such as polycyclic fused nitrochromenes 21 as well as pyridopsoralens 22 and 23. All these novel scaffolds are interesting structures with potential medicinal applications, and

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

• ][19][20]. There are several types of transition-metal-catalyzed C(sp3)−H halogenation reactions reported in the literature (Scheme 1b–d). Transition-metal-catalyzed 1,5-hydrogen atom transfer (1,5-HAT) is effective for promoting regioselective C(sp3)−H halogenation reactions (Scheme 1b) [21][22][23

• ]. The regioselectivity is controlled by the formation of a six-membered cyclic intermediate. Directing-group-assisted C(sp3)−H halogenation reactions are efficient for promoting regioselective C(sp3)−H halogenations (Scheme 1c) [24][25][26][27][28]. In these reactions, the C(sp3)–H bond at the β

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

• exploring the MC-MWA reactions Jiang and co-workers [41] designed a microwave facilitated regioselective four-component domino reaction employing naphthyl- or anthracenylamine 10, aldehydes 5 and 2-hydroxy-1,4-naphthoquinone (11) in acetic acid for the construction of dibenzo[a,h]acridine-12,13(7H,14H

• marketed drugs structured around indole implying its pharmacological significance such as oxypertine (27), ateviridine (28) [47] and spirooxindole-based potent cytotoxic agents 29, 30 and 31 [48]. In 2017, Lin and co-workers [49] designed a TFA-catalyzed three-component reaction for the regioselective

• regioselective construction of substituted 5-aza-adenines 113 using cyanamide (110), triethyl orthoformate (111) and 5-amino-1,2,4-triazoles 112 as structural units with methanol as solvent (Scheme 42). Simple filtration with no product isomer formation gives this protocol an edge over the other traditional

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

• formation of an unexpected product, i.e., β-triazolylenone. Being inspired by the results, we intended to use 1,3-dicarbonyl compounds as detosylative alkylating agents that would lead to the formation of β-triazolylenones in a highly regioselective manner under mild conditions (Scheme 1d). Results and

• with cyclic 1,3-diketones to form various β-triazolylenones. Although the scope of the 1,3-dicarbonyl compound is limited, the protocol is very convenient and useful as it employs very mild reaction conditions. It is also highly regioselective and `affords only N1-alkylated products in moderate to

Designed whole-cell-catalysis-assisted synthesis of 9,11-secosterols

• Marek Kõllo,
• Marje Kasari,
• Villu Kasari,
• Tõnis Pehk,
• Ivar Järving,
• Margus Lopp,
• Arvi Jõers and
• Tõnis Kanger

Beilstein J. Org. Chem. 2021, 17, 581–588, doi:10.3762/bjoc.17.52

• chemistry and synthetic biology. Stereo- and regioselective hydroxylation at C9 (steroid numbering) is carried out using whole-cell biocatalysis, followed by the chemical cleavage of the C–C bond of the vicinal diol. The two-step method features mild reaction conditions and completely excludes the use of

• have presented the results of the synthesis of the 9,11-secosteroid carbon skeleton by using the designed whole-cell biotransformation of natural steroids with a genetically engineered biocatalyst. The enzymatic oxidation of cortisol derivatives is completely stereo- and regioselective, affording only

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

• simplicity of the developed protocol. The current transformation was also found to be compatible for the late-stage modification of natural products. Keywords: amination; heteroarylation; quinoline N-oxides; regioselective; triazoles; Introduction Quinoline is a key heterocyclic moiety found in many

• derivatives is highly desired. The continuous interest and efforts of our group for the derivatization of quinoline moieties [57] and use of N-sulfonyl-1,2,3-triazoles as heterocyclic precursors encouraged us to develop a new strategy for the regioselective C2-triazolylation of quinoline N-oxide under mild

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

• (CuAAC) reaction provides the target product IV (Scheme 1, pathway A) [59][60][61]. Pathway B is designed on the basis of our group investigations on the synthesis of 2,6-bistriazolylpurine derivatives and their application in reactions with N-, S- and P-nucleophiles making use of regioselective SNAr

Mesoionic tetrazolium-5-aminides: Synthesis, molecular and crystal structures, UV–vis spectra, and DFT calculations

• Vladislav A. Budevich,
• Sergei V. Voitekhovich,
• Alexander V. Zuraev,
• Vadim E. Matulis,
• Vitaly E. Matulis,
• Alexander S. Lyakhov,
• Ludmila S. Ivashkevich and
• Oleg A. Ivashkevich

Beilstein J. Org. Chem. 2021, 17, 385–395, doi:10.3762/bjoc.17.34

• hydrochloric acid. Indeed, the de-tert-butylation was found to be regioselective leading to the 2-tert-butyltetrazole (12a) and 1-methyltetrazole (12b) derivatives, respectively (Scheme 2). The selectivity of the reaction was confirmed by a 13C NMR shift comparison for the C5 endocyclic atoms of tetrazoles 12a

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

• amines 178a–c, the corresponding hemiaminal ethers 179a–c were obtained (Scheme 43). The reaction is highly regioselective as no methoxylation of 178a and 178b was observed on the nontrifluoromethylated alkyl substituent (Me or Et). Hence, although amines 178a–c are more difficult to oxidize than their

Regioselective chemoenzymatic syntheses of ferulate conjugates as chromogenic substrates for feruloyl esterases

• Olga Gherbovet,
• Fernando Ferreira,
• Apolline Clément,
• Mélanie Ragon,
• Julien Durand,
• Sophie Bozonnet,
• Michael J. O'Donohue and
• Régis Fauré

Beilstein J. Org. Chem. 2021, 17, 325–333, doi:10.3762/bjoc.17.30

• regioselective functionalization of 4-nitrocatechol and enzymatic transferuloylation. The use of this strategy to characterize type A feruloyl esterase from Aspergillus niger reveals the advantages of this substrate for the characterizations of feruloyl esterases. Keywords: esterase; feruloylated conjugates

• chromogenic 5-O-feruloylated α-ʟ-arabinofuranosides 1a and 1b is usually achieved using a multistep pathway that involves trapping the furanose conformation, anomeric activation, glycosidation, regioselective deprotection of the primary hydroxy group, feruloylation, and final deprotection to yield the target

• molecule [12][15][16][17]. Additionally, the temporary protection of the functional groups is sometimes used during the synthesis in order to facilitate certain steps. Using an alternative approach, we employed a one-step regioselective transesterification of the unprotected vinyl ferulate 2 (synthesized

Hydrazides in the reaction with hydroxypyrrolines: less nucleophilicity – more diversity

• Dmitrii A. Shabalin,
• Evgeniya E. Ivanova,
• Igor A. Ushakov,
• Elena Yu. Schmidt and
• Boris A. Trofimov

Beilstein J. Org. Chem. 2021, 17, 319–324, doi:10.3762/bjoc.17.29

• saturated pyridazine scaffolds is both highly topical and necessary. Recently, we have developed a convenient approach to the 1,4-dihydropyridazine core based on the Brønsted acid-catalyzed regioselective recyclization of 5-hydroxypyrrolines (assembled in a one-pot manner from ketoximes and acetylene gas [8

The preparation and properties of 1,1-difluorocyclopropane derivatives

• Kymbat S. Adekenova,
• Peter B. Wyatt and
• Sergazy M. Adekenov

Beilstein J. Org. Chem. 2021, 17, 245–272, doi:10.3762/bjoc.17.25

• -difluoro-1-alkenylcyclopropanes 90–92 (Scheme 41) [88]. All three compounds underwent a highly regioselective cleavage of the C1–C3 bond. Hence, the major products of all rearrangements were produced via [1,3]-sigmatropic shifts (Scheme 41). The products were the result of the breaking of the C–C bond

• -difluorocyclopropanes in the synthesis of fluoroalkenyl-substituted compounds (monofluoroalkenes) have been actively studied. Great opportunities exist for the use of transition metal catalysis. The catalytic hydrogenolysis of 1,1-difluoro-3-methyl-2-phenylcyclopropane (151) led to the regioselective C2–C3 distal bond

1,2,3-Triazoles as leaving groups in S_NAr–Arbuzov reactions: synthesis of C6-phosphonated purine derivatives

• Kārlis-Ēriks Kriķis,
• Irina Novosjolova,
• Anatoly Mishnev and
• Māris Turks

Beilstein J. Org. Chem. 2021, 17, 193–202, doi:10.3762/bjoc.17.19

• a mixture of hexane and DCM using the slow-evaporation technique (Figure 2). This follows the previously reported regioselective C6-substitution of 2,6-bistriazolylpurines in SNAr transformations. Conclusion We have developed a novel SNAr–Arbuzov transformation that makes use of 1,2,3-triazole as a

• sluggish in substitution reactions with NaN3, and the burdensomely obtained (2-azido-9H-purin-6-yl)phosphonates fail to undergo CuAAC reactions. The developed SNAr–Arbuzov reaction between 2,6-bistriazolylpurine derivatives and trialkyl phosphites is C6-regioselective, as proved by single-crystal X-ray

Progress in the total synthesis of inthomycins

• Bidyut Kumar Senapati

Beilstein J. Org. Chem. 2021, 17, 58–82, doi:10.3762/bjoc.17.7

• transformed into (−)-101 using a three-step sequence. Upon iodination of (−)-101 produced iodide (+)-102 in excellent yield. Deiodination of (+)-102 followed by regioselective dihydroxylation with Sharpless’ AD mix-β reagent [64][65] provided diol (−)-103 as a mixture of stereoisomers. Significantly, the diol

Recent progress in the synthesis of homotropane alkaloids adaline, euphococcinine and N-methyleuphococcinine

• Dimas J. P. Lima,
• Antonio E. G. Santana,
• Michael A. Birkett and
• Ricardo S. Porto

Beilstein J. Org. Chem. 2021, 17, 28–41, doi:10.3762/bjoc.17.4

• desired homotropane. Ikeda synthesis – 2002 Ikeda et al. prepared azabicycle (±)-42, a protected form of (±)-euphococcinine (2) [45]. The author’s method focused on the radical reaction of 2-(but-3-ynyl)piperidine (±)-34 mediated by Bu3SnH. This "6-exo-dig" cyclization occurred in a regioselective way to

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

• than C-3’, which results in the regioselective formation of intermediate C. Cyclization of intermediate C gives D and subsequent proton transfer produces isomer E. It undergoes elimination to afford the annulation product 103 and the phosphine catalyst A is regenerated. In the same work, Lu and co

Regioselective synthesis of heterocyclic N-sulfonyl amidines from heteroaromatic thioamides and sulfonyl azides

• Vladimir Ilkin,
• Vera Berseneva,
• Tetyana Beryozkina,
• Tatiana Glukhareva,
• Lidia Dianova,
• Wim Dehaen,
• Eugenia Seliverstova and
• Vasiliy Bakulev

Beilstein J. Org. Chem. 2020, 16, 2937–2947, doi:10.3762/bjoc.16.243

• sulfonyl azides. Due to the high dipole moment, the presence of electronegative heteroatoms bearing electron lone pairs, one could propose alternative reactions which might make it difficult to find a general regioselective procedure for the synthesis of the target molecules in good yields. To the best of

• amino group. Thiatriazoles are known to be unstable compounds that readily evolve nitrogen and sulfur upon heating [56]. Conclusion We have shown that the reaction of sulfonyl azides with thioamides can serve as the basis for a general and efficient method for the regioselective synthesis of N-sulfonyl

Ultrasound-assisted Strecker synthesis of novel 2-(hetero)aryl-2-(arylamino)acetonitrile derivatives

• Emese Gal,
• Luiza Gaina,
• Hermina Petkes,
• Alexandra Pop,
• Castelia Cristea,
• Gabriel Barta,
• Dan Cristian Vodnar and
• Luminiţa Silaghi-Dumitrescu

Beilstein J. Org. Chem. 2020, 16, 2929–2936, doi:10.3762/bjoc.16.242

• -benzoxazole [13] or different other acetohydrazines [14], complexation of phenothiazinyl-chalcone using diiron nonacarbonyl [15], and regioselective oxidation [16]. α-Aminonitriles are versatile synthetic intermediates that are readily obtainable by a Strecker reaction involving the addition of a cyanide

Easy access to a carbohydrate-based template for stimuli-responsive surfactants

• Thomas Holmstrøm,
• Daniel Raydan and
• Christian Marcus Pedersen

Beilstein J. Org. Chem. 2020, 16, 2788–2794, doi:10.3762/bjoc.16.229

• with high regioselectivity via the Černý epoxide [20]. Results and Discussion Synthesis The synthesis was initiated by a regioselective esterification of levoglucosan (1) with tosyl chloride in pyridine, first presented by Černý and co-workers, in order to afford the 1,6-anhydro-2,4-di-O-tosyl-β-ᴅ

Synthesis of purines and adenines containing the hexafluoroisopropyl group

• Viacheslav Petrov,
• Rebecca J. Dooley,
• Alexander A. Marchione,
• Elizabeth L. Diaz,
• Brittany S. Clem and
• William Marshall

Beilstein J. Org. Chem. 2020, 16, 2739–2748, doi:10.3762/bjoc.16.224

• products in 47–78% yield. While for purine and 4- and 5-azabenzimidazole, the reaction led to a mixture of two isomers, the reaction of adenine and the corresponding 2-fluoro derivative was regioselective, resulting in the formation of only one isomer in each case. The alkylation of theophylline led to the

Selective and reversible 1,3-dipolar cycloaddition of 6-aryl-1,5-diazabicyclo[3.1.0]hexanes with 1,3-diphenylprop-2-en-1-ones under microwave irradiation

• Alexander P. Molchanov,
• Mariia M. Efremova,
• Mariya A. Kryukova and
• Mikhail A. Kuznetsov

Beilstein J. Org. Chem. 2020, 16, 2679–2686, doi:10.3762/bjoc.16.218

• liberation of the aromatic aldehyde and formation of the new azomethine imines. Conclusion The cycloaddition of azomethine imines, generated from 6-aryl-1,5-diazabicyclo[3.1.0]hexanes under microwave heating, with 1,3-diarylpropenones occurs regioselective with the formation of 2-benzoyl-substituted pyrazolo

Hierarchically assembled helicates as reaction platform – from stoichiometric Diels–Alder reactions to enamine catalysis

• David Van Craen,
• Jenny Begall,
• Johannes Großkurth,
• Leonard Himmel,
• Oliver Linnenberg,
• Elisabeth Isaak and
• Markus Albrecht

Beilstein J. Org. Chem. 2020, 16, 2338–2345, doi:10.3762/bjoc.16.195

• providing the stereoinformation necessary for induction during the C–C bond formation. Catalytic approaches for C–C bond-forming reactions even found their way into the relatively young field of supramolecular chemistry, e.g., regioselective Diels–Alder reactions within supramolecular hosts as described by

Formation of an exceptionally stable ketene during phototransformations of bicyclo[2.2.2]oct-5-en-2-ones having mixed chromophores

• Asitanga Ghosh

Beilstein J. Org. Chem. 2020, 16, 2297–2303, doi:10.3762/bjoc.16.190

• like phenyl or isopropenyl at the bridgehead position were analyzed for the first time in different solvents and upon irradiation with different wavelengths. In all cases, a regioselective photoinduced 1,5-phenyl migration leading to vinyl ketenes from the more congested site of the molecule to the

• photoreactions of bridged bicyclic systems like 3a–g were carried out [9][10][11][12][13]. These molecules contain a δ-keto-α,β-enone system juxtaposed with a (cis)-dibenzoylalkene moiety. Interestingly, photoreactions of 3a–f were found to follow regioselective photoindiuced 1,5-phenyl migration from the more

• ]. Photoreaction of 7a and 7b Irradiation of a degassed solution of 7a,b in benzene at 254 nm for 3–4 h yielded a pale yellow solid of ketene 10a,b (Scheme 5, Table 2) through regioselective photoinduced 1,5-phenyl migration and we did not obtain any 1,2-AS or any other photoproduct. The same ketenes were isolated

Synthetic approaches to bowl-shaped π-conjugated sumanene and its congeners

• Shakeel Alvi and
• Rashid Ali

Beilstein J. Org. Chem. 2020, 16, 2212–2259, doi:10.3762/bjoc.16.186

• performed the similar transformation in almost identical yield using Swern oxidation reaction conditions. The diketone 19 was then transformed into the enantiopure iodonorbornanone 22 in three steps which on further regioselective Pd-catalyzed cyclotrimerization furnished the syn-benzocyclotrimer 23 in 55

• mono-substituted sumanene derivatives 49b–d in a stereoselective manner as can be inspected from Scheme 10 [41][42]. In another event, Amaya, Ito, Katoh and Hirao reported a vital building block 53 to extend the π-conjugation bidirectionally through regioselective functionalization (Scheme 11) [43]. To

Regioselective cobalt(II)-catalyzed [2 + 3] cycloaddition reaction of fluoroalkylated alkynes with 2-formylphenylboronic acids: easy access to 2-fluoroalkylated indenols

• Tatsuya Kumon,
• Miroku Shimada,
• Jianyan Wu,
• Shigeyuki Yamada and
• Tsutomu Konno

Beilstein J. Org. Chem. 2020, 16, 2193–2200, doi:10.3762/bjoc.16.184

• -fluoroalkylated indenols, together with a very small amount of 3-fluoroalkylated indanones as side products. Keywords: [2 + 3] cycloaddition; cobalt catalyst; fluorine-containing; indenols; regioselective; Introduction 2,3-Disubstituted indenol derivatives are important compounds possessing high potential due