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

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

• ] cycloaddition [17] of enone 95 and tert-butyl 2-butynoate (96) with PBu3 and K2CO3/MeOH as additive to give the cycloaddition adduct 97 in 83% yield [43] (Scheme 6C). A seven-step synthesis from 97 gave pentacyclic ketone 98. Pentacyclic ketone 98 was exposed to PTSA under reflux to give the Wagner–Meerwein

Chiral anion recognition using calix[4]arene-based ureido receptors in a 1,3-alternate conformation

• Tereza Horáčková,
• Jan Budka,
• Vaclav Eigner,
• Wen-Sheng Chung,
• Petra Cuřínová and
• Pavel Lhoták

Beilstein J. Org. Chem. 2020, 16, 2999–3007, doi:10.3762/bjoc.16.249

• exemplified by our previously published receptors C1 based on a calix[4]arene moiety or by C2 using thiacalix[4]arene as the core scaffold [44][45]. Moreover, the introduction of the tert-butyl groups into the 1,3-alternate conformer should lead to the overall increase rigidity of the molecule, possibly

• already established by our previous receptors C1 and C2 (Figure 1) [44][45], although the direct comparison with our novel results is rather difficult due to the different types of derivatives (C1 has a cavity without tert-butyl groups, and C2 is based on thiacalix[4]arene). Nevertheless, the simultaneous

Naphthalonitriles featuring efficient emission in solution and in the solid state

• Sidharth Thulaseedharan Nair Sailaja,
• Iván Maisuls,
• Jutta Kösters,
• Alexander Hepp,
• Andreas Faust,
• Jens Voskuhl and
• Cristian A. Strassert

Beilstein J. Org. Chem. 2020, 16, 2960–2970, doi:10.3762/bjoc.16.246

• scattering (DLS). The steady-state and time-resolved photoluminescence spectroscopy studies revealed that all the molecules show intense fluorescence both in solution and in the aggregated state. In THF solutions, a blue emission was observed for the unsubstituted (H), methyl- (Me) and tert-butyl- (t-Bu

• systematically. The exemplar with a simple phenyl group is represented as H and the molecules that are substituted with methyl-, tert-butyl-, methoxy-, methylsulfanyl- and dimethylamino groups are abbreviated as Me, t-Bu, OMe, SMe and NMe2, respectively (Scheme 1). The design is based on the following

• absorption maxima experience a progressive red-shift by increasing the electron-donating ability of the substituents (Figure 3 and Table 1). This is especially true for the most red-shifted maximum, which corresponds to the transition into the lowest singlet state. We observe that the tert-butyl- and methyl

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

• the 1,4-dicarbonyl compounds [34][35], γ-carbonyl tert-butyl peroxides [36], and dihydrofurans [37] have also been reported to construct the pyrrole skeletons through this type of annulation; and (iii) [1 + 2 + 2] annulation, in which (hetero)arylamines are reacted with two different molecules, and

Bifurcated synthesis of methylene-lactone- and methylene-lactam-fused spirolactams via electrophilic amide allylation of γ-phenylthio-functionalized γ-lactams

• Tetsuya Sengoku,
• Koki Makino,
• Ayumi Iijima,
• Toshiyasu Inuzuka and
• Hidemi Yoda

Beilstein J. Org. Chem. 2020, 16, 2769–2775, doi:10.3762/bjoc.16.227

• initially treated the hydroxylactam prepared through CuBr-mediated hydroxylation of 3b with di-tert-butyl dicarbonate (Boc2O) in the presence of N,N-dimethyl-4-aminopyridine (DMAP), but a mixture of structurally unidentified products was formed. Meanwhile, when the reaction was carried out with 2.0

Enzyme-instructed morphological transition of the supramolecular assemblies of branched peptides

• Dongsik Yang,
• Hongjian He and
• Bing Xu

Beilstein J. Org. Chem. 2020, 16, 2709–2718, doi:10.3762/bjoc.16.221

• synthesis (SPPS) [47] to produce the peptides shown in Scheme 1. We first synthesized the peptide segments (i.e., Fmoc-DEDDDLLIG (1a) and acetyl-DEDDDLLIG (2a)). We kept the tert-butyl protecting groups of aspartic acid for the coupling reaction with Nap-ffky. We used 2,2,2-trifluoroethanol (TFE) in

• , we used TFA at room temperature for 2 h to cleave the tert-butyl protecting groups of 1b and 2b. After adding diethyl ether to precipitate the crude peptides, centrifugation, and washing three times, we used reversed-phase HPLC and acetonitrile (containing 0.1% TFA) and double-distilled water

Asymmetric Mannich reactions of (S)-N-tert-butylsulfinyl-3,3,3-trifluoroacetaldimines with yne nucleophiles

• Ziyi Li,
• Li Wang,
• Yunqi Huang,
• Haibo Mei,
• Hiroyuki Konno,
• Hiroki Moriwaki,
• Vadim A. Soloshonok and
• Jianlin Han

Beilstein J. Org. Chem. 2020, 16, 2671–2678, doi:10.3762/bjoc.16.217

• mode of nucleophilic attack on the imine double bond in 1. As presented in Figure 3, imine 1 might react in the most stable conformation with the bulky tert-butyl group pointing away from the imine double bond. In this case the only stereocontrolling factor in play is the difference between the

• the tert-butyl group but, as a major factor, the corresponding chelated transition states. As all diastereomers 3 can be easily isolated in optical pure form by routine column chromatography, this reaction should be of certain value for biological studies. In this regard, we decided to demonstrate the

Synthesis of 4-substituted azopyridine-functionalized Ni(II)-porphyrins as molecular spin switches

• Jannis Ludwig,
• Tobias Moje,
• Fynn Röhricht and
• Rainer Herges

Beilstein J. Org. Chem. 2020, 16, 2589–2597, doi:10.3762/bjoc.16.210

• cleavage of the methyl 3-mercaptopropionate under the Suzuki conditions. Nevertheless, azopyridines 14, 18 and 20 were converted almost quantitatively to the corresponding cross-coupling products, while the yield with 21 to 1j is only 52%. The tert-butyl protection group on 1f was cleaved according to a

• procedure of Nishimura et al. using mercury acetate in trifluoroacetic acid and anisole as radical scavenger (Scheme 5) [34]. Cleavage of the tert-butyl protection group yielded the disulfide 1g, which was reduced with catecholborane in tetrahydrofuran to give the free thiol 1h, which readily reoxidizes

Catalytic trifluoromethylation of iodoarenes by use of 2-trifluoromethylated benzimidazoline as trifluoromethylating reagent

• Tatsuhiro Uchikura,
• Nanami Kamiyama,
• Taisuke Ishikawa and
• Takahiko Akiyama

Beilstein J. Org. Chem. 2020, 16, 2442–2447, doi:10.3762/bjoc.16.198

• ’-positions were expected to be beneficial for the reaction, and other 4,4’-substituted bipyridyl ligands were investigated. We found that 4,4’-di-tert-butyl-2,2’-bipyridyl (4e) afforded the best result (91% yield). On the other hand, 2,2'-bipyridyl ligands bearing electron-donating (–OMe, 4f) and

A proposed sustainability index for synthesis plans based on input provenance and output fate: application to academic and industrial synthesis plans for vanillin as a case study

• John Andraos

Beilstein J. Org. Chem. 2020, 16, 2346–2362, doi:10.3762/bjoc.16.196

• descending order of impact according to OSI values given in Table 1: benzene (12.000), aniline (10.350), toluene (10.150), nitrobenzene (10.130), cyclohexane (8.777), diethyl ether (8.421), acetic anhydride (8.309), petroleum ether (7.734), ethyl acetate (7.597), N,N-dimethyltoluidine (7.592), methyl tert

• -butyl ether (7.365), dichloromethane (7.129), methanol (5.426), and ethanol (4.773). The Lampman plan had the highest overall RSGI value of 112,106 kg/kg vanillin due to the high masses of impactful solvents employed to obtain 1 kg of vanillin product, namely, nitrobenzene, diethyl ether, and

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

• -Maleimides 8a and 8b with a methyl and an ethyl residue showed higher yields and a lower induction in comparison to the benzyl derivative 8e with 43% ee and 39% ee (Table 1). The poorest result was obtained by using dienophile 8c with a tert-butyl substituent (82% yield, 18% ee). This maleimide gave the

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

• were treated with tert-butyl hydroperoxide (TBHP), two flanking benzene rings were found to be cleaved to afford 174 and 175 in impressive yields (Scheme 45) [82][83][84]. Moreover, they observed radical cations 172 and 173 formation when the same compounds were reacted with Br2 or 2,3,5,6-tetrafluoro

Lipophilicity trends upon fluorination of isopropyl, cyclopropyl and 3-oxetanyl groups

• Benjamin Jeffries,
• Zhong Wang,
• Robert I. Troup,
• Anaïs Goupille,
• Jean-Yves Le Questel,
• Charlene Fallan,
• James S. Scott,
• Elisabetta Chiarparin,
• Jérôme Graton and
• Bruno Linclau

Beilstein J. Org. Chem. 2020, 16, 2141–2150, doi:10.3762/bjoc.16.182

• adjacent acid/base groups. Importantly, it also leads to a lipophilicity reduction, as illustrated by the Hansch π-values of isopropyl (1.53) [13] and cyclopropyl (1.14) [14]. This compares to π = 1.98 for a tert-butyl group [13]. However, exceptions are known, as illustrated for 1 and 2 (Figure 1) [15

Access to highly substituted oxazoles by the reaction of α-azidochalcone with potassium thiocyanate

• Mysore Bhyrappa Harisha,
• Pandi Dhanalakshmi,
• Rajendran Suresh,
• Raju Ranjith Kumar and
• Shanmugam Muthusubramanian

Beilstein J. Org. Chem. 2020, 16, 2108–2118, doi:10.3762/bjoc.16.178

• , the reaction of 1m with potassium thiocyanate 2 under the optimal conditions in the presence of TEMPO furnished azirine and TEMPO, while the same reaction in the presence of BHT afforded the BHT-coupled thiocyanate product (SO-(2,6-di-tert-butyl-4-methylphenyl) (thioperoxocyanate)). These observations