Silica gel and microwave-promoted synthesis of dihydropyrrolizines and tetrahydroindolizines from enaminones

• Robin Klintworth,
• Garreth L. Morgans,
• Stefania M. Scalzullo,
• Charles B. de Koning,
• Willem A. L. van Otterlo and
• Joseph P. Michael

Beilstein J. Org. Chem. 2021, 17, 2543–2552, doi:10.3762/bjoc.17.170

• well as tert-butyl as precursors for the silica gel-mediated cyclization reaction to form pyrrolizine products. The bromomethyl ketones required for the initial sulfide contraction were either purchased from commercial suppliers or prepared from the corresponding methyl ketones by reported procedures

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

• of compounds 14a–f can be found in Supporting Information File 1. UV cyclization of oxime ester derivatives: general procedure A quartz UV reactor was charged with oxime ester and tert-butyl alcohol (5 mL) and the solution was degassed for 30 min. The solution was then subjected to UV irradiation

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

• therefore greatly benefit our procedure. The in situ formation of the aryldiazonium salt from the corresponding aniline and tert-butyl nitrite in methanol and subsequent exposure to green light in the presence of 2,5-dichlorobenzoquinone (1) proved to generate the desired product in yields that were similar

Base-free enantioselective S_N2 alkylation of 2-oxindoles via bifunctional phase-transfer catalysis

• Mili Litvajova,
• Emiliano Sorrentino,
• Brendan Twamley and
• Stephen J. Connon

Beilstein J. Org. Chem. 2021, 17, 2287–2294, doi:10.3762/bjoc.17.146

• investigating the behaviour of different alkylating agents (Table 2). Reactions with alkylating agents with increased steric demand provided products in higher ee (compare Table 2, entries 1, 2 and 3); with 3,5-bis(tert-butyl)benzyl bromide allowing the isolation of oxindole 10Ac in 92% yield and 84% ee. The

• -alkylated with bromo ester 13. The formed product (i.e., 14) was first amidated and then cyclised using benzylamine 11 to generate spirooxindole 15 in 54% yield and 94% ee. Chlorination with NCS, followed by tert-butyl ester cleavage in TFA/CH2Cl2 provided the final bioactive compound 6 in 93% ee

Photoredox catalysis in nickel-catalyzed C–H functionalization

• Lusina Mantry,
• Rajaram Maayuri,
• Vikash Kumar and
• Parthasarathy Gandeepan

Beilstein J. Org. Chem. 2021, 17, 2209–2259, doi:10.3762/bjoc.17.143

• -amino C(sp3)–H bonds using di-tert-butyl peroxide (DTBP) or dicumyl peroxide (DCP) as the methyl source under mild conditions [93]. Based on the substrate structure and peroxide choice, the authors developed four sets of reaction conditions (Scheme 29) [93]. In these reaction conditions, photocatalyst

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

• protocol (Scheme 7). The synthesis of the key building blocks 2-aminoazulene (24), 2-amino-6-bromoazulene (26), and its corresponding carbamate, tert-butyl N-(6-bromoazulen-2-yl)carbamate (27), used in their synthesis is presented in Scheme 7A. The carbamate 27 was subjected to a Buchwald–Hartwig reaction

• of directly connected 4,7-polyazulenes 18–20. Synthesis of (A) tert-butyl N-(6-bromoazulen-2-yl)carbamate (27), (B) dimeric aminoazulene 29, and (C) poly[2,6-aminoazulene] 31. Synthesis of poly{1,3-bis[2-(3-alkylthienyl)]azulene} 33–38. Synthesis of polymer ruthenium complexes 40–43. Synthesis of 4,7

Constrained thermoresponsive polymers – new insights into fundamentals and applications

• Patricia Flemming,
• Alexander S. Münch,
• Andreas Fery and
• Petra Uhlmann

Beilstein J. Org. Chem. 2021, 17, 2123–2163, doi:10.3762/bjoc.17.138

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