Asymmetric organocatalyzed synthesis of coumarin derivatives

• Natália M. Moreira,
• Lorena S. R. Martelli and
• Arlene G. Corrêa

Beilstein J. Org. Chem. 2021, 17, 1952–1980, doi:10.3762/bjoc.17.128

• was described by Sun et al. [46]. In this method, the catalyst (DHQ)2PYR 42 reacts with tert-butyl 2-bromoacetate, and then an ylide is formed by the base Cs2CO3. After a conjugated addition of this intermediate to the coumarin 43 followed by nucleophilic substitution, the corresponding cyclopropa[c

Regioselective N-alkylation of the 1H-indazole scaffold; ring substituent and N-alkylating reagent effects on regioisomeric distribution

• Ryan M. Alam and
• John J. Keating

Beilstein J. Org. Chem. 2021, 17, 1939–1951, doi:10.3762/bjoc.17.127

• observed > 99% N-1 regioselectivity for 3-carboxymethyl, 3-tert-butyl, 3-COMe, and 3-carboxamide indazoles. Further extension of this optimized (NaH in THF) protocol to various C-3, -4, -5, -6, and -7 substituted indazoles has highlighted the impact of steric and electronic effects on N-1/N-2 regioisomeric

On the application of 3d metals for C–H activation toward bioactive compounds: The key step for the synthesis of silver bullets

• Renato L. Carvalho,
• Amanda S. de Miranda,
• Mateus P. Nunes,
• Roberto S. Gomes,
• Guilherme A. M. Jardim and
• Eufrânio N. da Silva Júnior

Beilstein J. Org. Chem. 2021, 17, 1849–1938, doi:10.3762/bjoc.17.126

• usually mediated by V(V) and V(IV)-oxo-peroxo complexes, which are produced in situ from vanadium-oxo and dioxo precatalysts in the presence of oxidants, such as H2O2, O2, and tert-butyl hydroperoxide (TBHP) [76][77][78][79][80][81][82]. Inorganic acids and chelating and non-chelating carboxylic acids

Development of N-F fluorinating agents and their fluorinations: Historical perspective

• Teruo Umemoto,
• Yuhao Yang and
• Gerald B. Hammond

Beilstein J. Org. Chem. 2021, 17, 1752–1813, doi:10.3762/bjoc.17.123

• )-27-6. Enantioselective fluorinations of typical enolates were then performed (Scheme 63). The (R)-27-6 reagent gave up to 79% yield and 88% enantiomeric excess in the case of 2-benzyl-α-tetralone. 1-28. (R)- and (S)-N-fluoro-3-tert-butyl-7-nitro-benzothiazine 1,1-dioxides and spiro-type analogues In

• 2000, the Takeuchi group reported their second series of chiral N-fluorosultam reagents, (R)- and (S)-N-fluoro-3-tert-butyl-7-nitro-3,4-dihydro-2H-benzo[e][1,2]thiazine 1,1-dioxides 28-3 [93] (Scheme 64). Racemic 28-1 reacted with (+)-10-camphorsulfonyl chloride to give a mixture of the diastereomers

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

• good antitumor activity in comparison to 5-stibanotriazoles, this reinforces the importance of synthesizing 5-stibanotriazoles [54]. A similar reaction for the regioselective synthesis of triazole disulfides 98 through a copper(I)-catalyzed cycloaddition of azides 95, alkynes 96, and tert-butyl tosyl

• catalyst-free conditions. A series of azidobenzenesulfonamides 101 was first synthesized from commercially available orthanilic acid by a three-step procedure and then submitted to cycloaddition with different alkynes 102 using CuI and Cu as copper source, tris([1-(tert-butyl)-1H-1,2,3-triazol-4-yl]methyl

• treated with aryl and aliphatic alkyne partners and then with tert-butyl and cyclohexyl isocyanide to give 1,2,3‐triazole-fused oxazines 152. The reaction was extended to 2‐(azidophenyl)methanol species 150, which were treated with ethynylbenzene and cyclohexyl isocyanide, and in all cases, the

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

• were carried out in different organic solvents (Figure 3). The representative γ-carboline derivative tert-butyl-5-methyl-1-(1-methyl-1H-indol-2-yl)-5H-pyrido[4,3-b]indole-3-carboxylate (3ac) revealed similar absorption features with a shift in absorption maximum in different solvents. The highest

Double-headed nucleosides: Synthesis and applications

• Vineet Verma,
• Jyotirmoy Maity,
• Vipin K. Maikhuri,
• Ritika Sharma,
• Himal K. Ganguly and
• Ashok K. Prasad

Beilstein J. Org. Chem. 2021, 17, 1392–1439, doi:10.3762/bjoc.17.98

• reaction of 3,5-di-tert-butyl-1,2-benzoquinone with 5′-amino-5′-deoxy-2′,3′-O-isopropylideneuridine (67) and 5′-amino-2′,5′-dideoxyadenosine (70). The unprotected double-headed nucleoside (R)-N1-(4-(4,6-di-tert-butylbenzoxazol-2-yl)-β-ᴅ-erythrofuranosyl)uracil (69) was obtained by acidic hydrolysis of the

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

• recyclability, broad substrate scope, and high functional group tolerance (Scheme 1). Results and Discussion Our initial investigation focused on the CN-K photocatalyzed cascade alkyl radical addition/cyclization reaction of the N-arylallylamine 1a with tert-butyl N-hydroxyphthalimide (NHPI) ester (2a), a

Structural effects of meso-halogenation on porphyrins

• Keith J. Flanagan,
• Maximilian Paradiz Dominguez,
• Zoi Melissari,
• Hans-Georg Eckhardt,
• René M. Williams,
• Dáire Gibbons,
• Caroline Prior,
• Gemma M. Locke,
• Alina Meindl,
• Aoife A. Ryan and
• Mathias O. Senge

Beilstein J. Org. Chem. 2021, 17, 1149–1170, doi:10.3762/bjoc.17.88

• only small variations in the percentage of contacts formed between compounds 16–18 with a marginal increase in the H···H and a decrease in C···H contacts in compound 19 due to the bulky tert-butyl groups (Supporting Information File 1, Figure S55). With regards to bond lengths, angles, and atom

• create two different packing patterns. The first is the head-to-head interactions directed through the chlorine atoms interacting with the tert-butyl hydrogens (Supporting Information File 1, Figure S58A). With the addition of a second beta halogen, this motif drastically changes to become a face-to-edge

• porphyrin dimer with a di-halogeno-substitution. Interestingly, this structure despite the extended dual-core and tilt of the porphyrin rings behaves quite like a 5,15-di-halo-substituted porphyrin. The bromine atoms are seen to interact with the tert-butyl and pyrrole hydrogen atoms in a head-to-tail

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

• mechanism operating in reactions involving Grignard reagents in noncoordinating solvents, such as toluene and dichloromethane, while an acyclic model [43] is common in organolithium compounds in solvents such as THF. In the cyclic model, the bulky tert-butyl group occupies an equatorial position due to

• stereochemical outcome of the cyclization considering that the stereoinduction is derived from the dipole–dipole repulsion of the sulfinyl imine, which places the tert-butyl group on the Si face, and thus the cycloaddition occurs from the less sterically hindered Re face. The cyclization process worked also in

• , because of the influence of the bulky tert-butyl in the most stable conformation of the sulfinyl imine (Scheme 30). The authors also demonstrated the synthetic utility of compounds 100. Their reaction with thionyl chloride in methanol produced removal of the sulfinyl group and formation of the

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

• addition (see mechanism, Scheme 4, vide infra). On the other hand, 4-tert-butyl analog 1d underwent the reaction smoothly to form the corresponding product 3d in 70% yield. However, due to the inconsistent results with cyclohexanedione 2a, further scope was investigated by employing cyclopentane-1,3-dione

[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

• cholesterol 44 and histamine 45. Scientific literature [97] reports a three-step continuous synthesis of [6,6]-tert-butyl phenyl-C61-butyrate 47 based on tert-butyl 4-benzoylbutyrate hydrazone in a microstructured flow reactor that eliminates the need for stage-by-stage isolation of intermediate products and

• .) Synthesis of fullerenylpeptides 23 and 24. The synthetic route to the water-soluble biologically active fullerene–peptide derivative 27. Serial synthesis of monophenylmethanofullerenes. Four-step synthesis of the [6,6]-tert-butyl phenyl-C61-butyrate 47. Synthesis of aminophenylfullerenes 49 and 51 based on

A new and efficient methodology for olefin epoxidation catalyzed by supported cobalt nanoparticles

• Lucía Rossi-Fernández,
• Viviana Dorn and
• Gabriel Radivoy

Beilstein J. Org. Chem. 2021, 17, 519–526, doi:10.3762/bjoc.17.46

• MgO and tert-butyl hydroperoxide (TBHP) as oxidant is presented. This CoNPs@MgO/t-BuOOH catalytic combination allowed the epoxidation of a variety of olefins with good to excellent yield and high selectivity. The catalyst preparation is simple and straightforward from commercially available starting

• greener oxidizing agents as molecular oxygen, hydrogen peroxide or tert-butyl hydroperoxide (TBHP) [14][15][16][17]. However, using any of these oxidants alone results in considerable low reactivity and selectivity in olefin epoxidation reactions. Thus, several transition-metal-based catalytic methods

• , we proposed a plausible mechanistic pathway involving a Co(II)/Co(III) couple species, as depicted in Scheme 1. We assume that tert-butyl hydroperoxide could react with Co(II) species on the surface of the catalyst leading to the formation of metal-oxy radical A. This intermediate could react with

Synthetic strategies of phosphonodepsipeptides

• Jiaxi Xu

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

• methyl or tert-butyl chloroacetate 192, and hydrogenolysis, the target phosphonodepsipeptides 194 were obtained (Scheme 35) [8][9][13]. Synthesis of phosphonodepsipeptides via phosphinylation of hydroxy esters with phosphonochloridites followed by oxidation Hammer’s group developed a new route to prepare

Synthesis of trifluoromethyl ketones by nucleophilic trifluoromethylation of esters under a fluoroform/KHMDS/triglyme system

• Yamato Fujihira,
• Yumeng Liang,
• Makoto Ono,
• Kazuki Hirano,
• Takumi Kagawa and
• Norio Shibata

Beilstein J. Org. Chem. 2021, 17, 431–438, doi:10.3762/bjoc.17.39

• ketones in moderate yields (56–63%) under basic conditions. The alkyl groups of tert-butyl (1f)- and cyclohexyl (1g)-substituted methyl benzoate derivatives, biphenyl benzoate (1h), and electron-donating 4-methoxybenzoate, were nicely transformed into aryl trifluoromethyl ketones in moderate to high

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

• -butyltetrazolium-5-aminide, its N,N’-ethylene-bridged bis-derivative and (1,3-di-tert-butyl-1H-tetrazol-3-ium-5-yl)(1-phenyl-1H-tetrazol-5-yl)amide by single crystal X-ray analysis. The structural and spectral features of the tetrazolium-5-aminides are discussed by using quantum-chemical calculations. Keywords

• the bistetrazolium-5-aminide 10. The reactions of aminides 8a and 8b with 5-methylsulfonyl-1-phenyltetrazole in the presence of sodium hydroxide in boiling acetonitrile yielded compounds 11a and 11b, respectively. Taking into account the possibility of removing the tert-butyl group in tetrazolium

• Table 3. As can be seen, a good agreement of the bond lengths is observed for each of the six bonds presented in Table 3, and the methyl- and tert-butyl derivatives show no differences. On the other hand, a comparison of the data in Table 2 and Table 3 reveals the following structural differences of the

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

• of the benzylic cation intermediate 48f↔48f’, stabilized by the phenyl group (Scheme 12b). Substrate 51, bearing a tert-butyl group in the para-position, was also submitted to solvolysis in labeled H218O, generating the labeled benzylic alcohol 18O-52 (Scheme 13). The solvolysis of 51 was found to be

• -tert-butyl alcohol (Scheme 14) [63]. No further decomposition was observed in this case, suggesting that the especially challenging perfluoro-tert-butylcarbenium ion 55 cannot be generated. Highly deactivated bis(trifluoromethyl)-substituted carbenium ions and their precursors were also explored in

Synthesis of legonmycins A and B, C(7a)-hydroxylated bacterial pyrrolizidines

• Wilfred J. M. Lewis,
• David M. Shaw and
• Jeremy Robertson

Beilstein J. Org. Chem. 2021, 17, 334–342, doi:10.3762/bjoc.17.31

• reported values are within 5 ppm of the calculated theoretical values. Melting points were recorded on a Griffin mp apparatus and are uncorrected. (S)-tert-Butyl 2-(2-cyanopropanoyl)pyrrolidine-1-carboxylate (16) To a solution of LHMDS (100 mL, 1.0 M in THF, 100 mmol), cooled to −78 °C and under a N2

¹⁹F NMR as a tool in chemical biology

• Diana Gimenez,
• Aoife Phelan,
• Cormac D. Murphy and
• Steven L. Cobb

Beilstein J. Org. Chem. 2021, 17, 293–318, doi:10.3762/bjoc.17.28

• their NMR study on lipid bicelles (Figure 2) [15]. In contrast to more traditional amino acids, such as 1–4, the perfluorinated tert-butyl moiety in 8 has nine equivalent fluorine atoms and no coupled hydrogens, so it gives rise to a characteristic high intensity 19F NMR singlet. As shown by the authors

Annulation of a 1,3-dithiole ring to a sterically hindered o-quinone core. Novel ditopic redox-active ligands

• Sergey V. Norkov,
• Anton V. Cherkasov,
• Andrey S. Shavyrin,
• Maxim V. Arsenyev,
• Viacheslav A. Kuropatov and
• Vladimir K. Cherkasov

Beilstein J. Org. Chem. 2021, 17, 273–282, doi:10.3762/bjoc.17.26

• ][10][11][12][13], whereas methods resulting in the synthesis of o-quinone analogs are scarce. Results and Discussion Previously we reported an efficient synthesis pathway for the annulation of the 1,3-dithiole cycle to the 4,5-positions of an o-quinone ring using the reaction of 3,6-di-tert-butyl-4

• reaction of 4,5-dichloro-3,6-di-tert-butyl-o-benzoquinone (4) [19] with alkali metal gem-dithiolates. This synthetic procedure allows us to significantly extend the range of substituents which could be potentially introduced to the final product. Gem-dithiolates are comparatively less studied than related

• Supporting Information File 1). At the same time, the plane of the six-membered o-quinone ring is slightly distorted in order to weaken the steric strain effects of the tert-butyl groups and neighboring carbonyl oxygens/dithiole sulfur atoms. Such distortion is typical of sterically hindered o-quinones and

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

• 3-oxobutanoates 1b–d reacted with sodium S-benzyl sulfurothioate (2a), the expected products 3k–m were obtained in only moderate yields (Table 2, entries 11–13). On the other hand, the reaction conducted using the tertiary-alkyl-substituted 3-oxobutanoate (1e) gave tert-butyl 2-(benzylthio)acetate

Novel library synthesis of 3,4-disubstituted pyridin-2(1H)-ones via cleavage of pyridine-2-oxy-7-azabenzotriazole ethers under ionic hydrogenation conditions at room temperature

• Romain Pierre,
• Anne Brethon,
• Sylvain A. Jacques,
• Aurélie Blond,
• Sandrine Chambon,
• Sandrine Talano,
• Catherine Raffin,
• Branislav Musicki,
• Claire Bouix-Peter,
• Loic Tomas,
• Gilles Ouvry,
• Rémy Morgentin,
• Laurent F. Hennequin and
• Craig S. Harris

Beilstein J. Org. Chem. 2021, 17, 156–165, doi:10.3762/bjoc.17.16

• morpholine amide 7. The synthesis started by selective SNAr reaction with 4 and tert-butyl ((cis)-4-aminocyclohexyl)carbamate affording the intermediate nicotinic acid 5 in 70% yield without the need for chromatography. Subsequent amide coupling using TBTU afforded 2-chloro precursor 6 in excellent yield

• conditions. To our surprise, the iodide at C-4 was selectively displaced to afford only 27. We propose that this observation can be explained by HSAB (hard-soft-acid-base) theory whereby the soft –OBt anion preferentially reacts at the soft C-4–I center [18]. As expected, reacting 26 first with tert-butyl

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

• phenol, p-methoxyphenol (1b) was used, the reaction proceeded to afford ether 2b in 79% yield (Table 2, entry 1). An ortho-substitution with the bulkier tert-butyl group slightly affected the reaction giving product 2c in still acceptable yield (47%, Table 2, entry 2). p-Nitrophenol (1d), which is an

Amine–borane complex-initiated SF₅Cl radical addition on alkenes and alkynes

• Audrey Gilbert,
• Pauline Langowski,
• Marine Delgado,
• Laurent Chabaud,
• Mathieu Pucheault and
• Jean-François Paquin

Beilstein J. Org. Chem. 2020, 16, 3069–3077, doi:10.3762/bjoc.16.256

• °C and at the tested reaction temperatures. The results in hexane, ethyl acetate (EtOAc), and methyl tert-butyl ether (MTBE) are shown in Table 1 and Table 2, but more solvents were tested and did not lead to higher yields of the desired compound (see Supporting Information File 1 for the complete