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

Syntheses of spliceostatins and thailanstatins: a review

• William A. Donaldson

Beilstein J. Org. Chem. 2020, 16, 1991–2006, doi:10.3762/bjoc.16.166

• (−)-51 (Scheme 6) [16]. An Achmatowicz oxidation [29] with tert-butyl hydroperoxide catalyzed by VO(acac)2 afforded the hemiketal 52, and the ionic reduction [22] of 52 gave the enone (−)-53. The enone transposition of 53 was effected by the addition of methyl-Grignard, followed by the oxidation with PCC

• . The removal of the silyl protecting group and hydrolysis of the methyl ester afforded the carboxylic acid 108. A subsequently attempted Suzuki–Miyaura coupling of 108 with vinyl boronates was described as “capricious”, and thus the acid was esterified with the tert-butyl donor reagent 109 to afford

• -metathesis of 121 with a five-fold excess of isopropenylboronic acid pinacol ester afforded the lynchpin vinylborane 130. A Pd-catalyzed Suzuki–Miyaura coupling of 130 with the vinyl iodide 110, 111, or 112 gave the tert-butyl ester 131, 132, or 133 in a moderate yield (42–63%). The hydrolysis of the tert

Metal-free synthesis of phosphinoylchroman-4-ones via a radical phosphinoylation–cyclization cascade mediated by K₂S₂O₈

• Qiang Liu,
• Weibang Lu,
• Guanqun Xie and
• Xiaoxia Wang

Beilstein J. Org. Chem. 2020, 16, 1974–1982, doi:10.3762/bjoc.16.164

• better product yields as compared with the reactions performed at either 70 °C or 90 °C (Table 1, entries 2, 16, and 17). Then, various oxidants such as (NH4)2S2O8, Na2S2O8, TBHP (tert-butyl hydroperoxide), DTBP (di-tert-butyl peroxide), and dioxygen were tested and the results showed that K2S2O8

Controlling the stereochemistry in 2-oxo-aldehyde-derived Ugi adducts through the cinchona alkaloid-promoted electrophilic fluorination

• Yuqing Wang,
• Gaigai Wang,
• Anatoly A. Peshkov,
• Ruwei Yao,
• Muhammad Hasan,
• Manzoor Zaman,
• Chao Liu,
• Stepan Kashtanov,
• Olga P. Pereshivko and
• Vsevolod A. Peshkov

Beilstein J. Org. Chem. 2020, 16, 1963–1973, doi:10.3762/bjoc.16.163

• components (Scheme 2). The product 8a obtained from benzoic acid, phenylglyoxal, benzylamine, and tert-butyl isocyanide was selected for the screening of the reaction parameters (Table 3). The overall process was conducted in a two-step one-pot fashion as was originally designed by Shibata. In the first step

• similarly to 8a were obtained from benzylamine and tert-butyl isocyanide by varying either acid or 2-oxo-aldehyde components revealed that it was difficult to achieve high enantioselectivity for such substrates. Specifically, none of the studied chiral promoters could afford the desired products 12b and 12c

• enantioselective induction was lower than in the reactions with the analogous tert-butyl isocyanide-derived substrate 8d. This could probably be ascribed to a reduced rigidity and bulkiness of the n-butyl group as compared to tert-butyl. For the substrates 8a–g tested with eight cinchona alkaloid derivatives

Design, synthesis and application of carbazole macrocycles in anion sensors

• Alo Rüütel,
• Ville Yrjänä,
• Sandip A. Kadam,
• Indrek Saar,
• Mihkel Ilisson,
• Astrid Darnell,
• Kristjan Haav,
• Tõiv Haljasorg,
• Lauri Toom,
• Johan Bobacka and
• Ivo Leito

Beilstein J. Org. Chem. 2020, 16, 1901–1914, doi:10.3762/bjoc.16.157

• reaction. Due to the highly acidic environment partial loss of one of the tert-butyl groups in 2 took place. This considerably reduced the yield and resulted in a mixture of products 3a and 3b that was challenging to separate due to similar properties. Careful optimization of the nitration process did not

• reference [6]. It is worth noting that the described cleavage problem during nitration was specific to tert-butyl groups. We also studied the possibility of hexyl substituents instead of tert-butyl groups [25]. In this case, the nitration process yielded only the desired product. However, since this

• possibility was investigated after the production of the first macrocycles bearing tert-butyl substituents, we decided to not switch substituents. The formation of macrocycles from 8 was achieved following two different synthetic strategies. For receptors MC003–MC010, amide bond formation was carried out

Stereoselective Biginelli-like reaction catalyzed by a chiral phosphoric acid bearing two hydroxy groups

• Xiaoyun Hu,
• Jianxin Guo,
• Cui Wang,
• Rui Zhang and
• Victor Borovkov

Beilstein J. Org. Chem. 2020, 16, 1875–1880, doi:10.3762/bjoc.16.155

• for the enantioselectivity (Table 2, entries 4–6, and 8) except for the sterically demanding tert-butyl group (Table 2, entry 12). Obviously, steric effects in the aromatic aldehydes played a key role for the enantioselectivity of the reaction. To further confirm the importance of two secondary free

On the hydrolysis of diethyl 2-(perfluorophenyl)malonate

• Ilya V. Taydakov and
• Mikhail A. Kiskin

Beilstein J. Org. Chem. 2020, 16, 1863–1868, doi:10.3762/bjoc.16.153

• of diethyl 2-(perfluorophenyl)malonate, acid-catalyzed reactions were also tested. Trifluoroacetic acid (TFA) is a common reagent for the catalytic cleavage of tert-butyl esters, but in the stoichiometric quantity it is also suitable for the cleavage of nonvolatile methyl or ethyl esters due to

• ) is not suitable for the preparation of 2-(perfluorophenyl)malonic acid (2), due to its thermal instability and strong tendency to decarboxylation. We believed, that di-tert-butyl 2-(perfluorophenyl)malonate or dibenzyl 2-(perfluorophenyl)malonate, which are cleaving under very mild conditions are

Clickable azide-functionalized bromoarylaldehydes – synthesis and photophysical characterization

• Dominik Göbel,
• Marius Friedrich,
• Enno Lork and
• Boris J. Nachtsheim

Beilstein J. Org. Chem. 2020, 16, 1683–1692, doi:10.3762/bjoc.16.139

• reactions (CuAAC). For this, we treated the azide-functionalized luminophores with alkynes exhibiting different degrees of steric demand, including 1-decyne (29), phenylacetylene (30), 1-ethynyladamantane (31) and 1,3-di-tert-butyl-5-ethynylbenzene (32, see Scheme 5). All triazoles 33–44, based on the

Synthesis of new dihydroberberine and tetrahydroberberine analogues and evaluation of their antiproliferative activity on NCI-H1975 cells

• Giacomo Mari,
• Lucia De Crescentini,
• Serena Benedetti,
• Francesco Palma,
• Stefania Santeusanio and
• Fabio Mantellini

Beilstein J. Org. Chem. 2020, 16, 1606–1616, doi:10.3762/bjoc.16.133

• ) to afford products 3a–n that were crystallized in a mixture of diethyl ether/petroleum ether. Characterization data of 3a, chosen as representative compound, are given below. tert-Butyl 2-(2-(9,10-dimethoxy-6,8,13,13a-tetrahydro-5H-[1,3]dioxolo[4,5-g]isoquinolino[3,2-a]isoquinolin-13-yl)-1

Azidophosphonium salt-directed chemoselective synthesis of (E)/(Z)-cinnamyl-1H-triazoles and regiospecific access to bromomethylcoumarins from Morita–Baylis–Hillman adducts

• Soundararajan Karthikeyan,
• Radha Krishnan Shobana,
• Kamarajapurathu Raju Subimol,
• J. Helen Ratna Monica and
• Ayyanoth Karthik Krishna Kumar

Beilstein J. Org. Chem. 2020, 16, 1579–1587, doi:10.3762/bjoc.16.130

• ). The synthetic utility of the reaction was further extended to ortho-vanillin and para-bromobenzaldehyde to afford the corresponding halomethylcoumarins (4b/c). However, this regiospecific transformation was restricted only to the MBH adducts derived from salicyladehydes and tert-butyl acrylate [52][53

Photocatalyzed syntheses of phenanthrenes and their aza-analogues. A review

• Alessandra Del Tito,
• Havall Othman Abdulla,
• Davide Ravelli,
• Stefano Protti and
• Maurizio Fagnoni

Beilstein J. Org. Chem. 2020, 16, 1476–1488, doi:10.3762/bjoc.16.123

• approach was based on the one-electron reduction of diazonium salts (see the case of 13.3+ in Scheme 13), formed in situ by the reaction of the chosen 2-heteroaryl aniline (e.g., 13.1) with tert-butyl nitrite (1.5 equiv). Formation of the aryl radical 13.4· and following addition onto an alkyne moiety (e.g

• developed, starting from sulfonyl hydrazines in place of sulfonyl chlorides. In this case, the RuII-based photocatalyst was able to reduce tert-butyl peroxybenzoate, triggering the release of a tert-butoxyl radical. This was in turn able to oxidize the hydrazine, allowing the liberation of the desired

The McKenna reaction – avoiding side reactions in phosphonate deprotection

• Katarzyna Justyna,
• Joanna Małolepsza,
• Damian Kusy,
• Waldemar Maniukiewicz and
• Katarzyna M. Błażewska

Beilstein J. Org. Chem. 2020, 16, 1436–1446, doi:10.3762/bjoc.16.119

• be accompanied by side reactions such as the cleavage of tert-butyl carboxyester, [14][15] or other ester groups [16], as well as the formation of decomposition products [17][18][19][20]. Instead of focusing only on the experiments that “did work”, we decided to follow an alternative strategy

• reaction with BTMS, and underwent exchange of the chlorine substituent for bromine. This reaction can be partially circumvented by using nonpolar solvents, amines and lower temperatures. Section 5: Cleavage of the tert-butyl carboxyester group BTMS is known for its chemoselectivity and cleaves phosphonate

• this study, we took a closer look at the reactivity upon exposure to BTMS of two types of carboxyester groups, the acid-labile tert-butyl and the relatively stable ethyl esters. For this we chose triethyl phosphonoacetate (8a), tert-butyl phosphonoacetate (8b) and its pyridine-3-ylmethyl analogs 9a,e

Recent synthesis of thietanes

• Jiaxi Xu

Beilstein J. Org. Chem. 2020, 16, 1357–1410, doi:10.3762/bjoc.16.116

• reaction of the first stable thiobenzaldehyde, 2,4,6-tri(tert-butyl)thiobenzaldehyde (211) with substituted allenes 212. Irradiation of thiobenzaldehyde 211 with RCR1=C=CH2 (212) gave diastereospecific [2 + 2] cycloadducts, thietanes 213 in 75–95% yields [67] (Scheme 41). In 1984, Coyle and Rapley

• photochemical [2 + 2] cycloaddition of tert-butyl 2-(5-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)acetate (322) and thiobenzophenone (184a) was applied to prepare thietane 323 as a model compound for photolyses in a comparative flavin-induced cleavage study of oxetanes and thietanes [89] (Scheme 60). 2,5

Synthesis, antiinflammatory activity, and molecular docking studies of bisphosphonic esters as potential MMP-8 and MMP-9 inhibitors

• Abimelek Cortes-Pacheco,
• María Adelina Jiménez-Arellanes,
• Francisco José Palacios-Can,
• José Antonio Valcarcel-Gamiño,
• Rodrigo Said Razo-Hernández,
• María del Carmen Juárez-Vázquez,
• Adolfo López-Torres and
• Oscar Abelardo Ramírez-Marroquín

Beilstein J. Org. Chem. 2020, 16, 1277–1287, doi:10.3762/bjoc.16.108

• order to explore the SAR in the proposed compounds 3–6, we evaluated the effect of the volume of the ester group by the inclusion of ethyl or tert-butyl substituents in the aliphatic derivatives 3 and 4. On the other hand, the replacement of the aliphatic chains by an aromatic portion led us to the

• [23]. Then, the above-named derivatives were synthesized in a first stage by the esterification of bromoacetyl bromide and the corresponding alcohol. The reaction of ethyl or tert-butyl alcohol and bromoacetyl bromide in the presence of triethylamine in CH2Cl2 yielded the bromoaceto esters 7 and 8 in

• the cavity of the enzyme in MMP-8, as shown in Figure 4. For the compounds 4 and 5, the tert-butyl and benzyl groups at the ester moiety were pointing out to the solvent, without any important interactions with the hydrophobic zone inside the cavity (Figure 4b and Figure 4c). The only molecule that

Oxime radicals: generation, properties and application in organic synthesis

• Igor B. Krylov,
• Stanislav A. Paveliev,
• Alexander S. Budnikov and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2020, 16, 1234–1276, doi:10.3762/bjoc.16.107

• , arylalkyl, and diaryl oxime radicals was also studied by EPR spectroscopy [53]. Radicals were generated under inert atmosphere directly in the EPR cavity by photolysis of the added di-tert-butyl peroxide (Scheme 1). The authors pointed out the complexity of the processes of iminoxyl radicals’ decomposition

• radical that did not undergo decomposition and dimerization in the solution for a time sufficient to use it as a reagent was the di-tert-butyliminoxyl radical (8) [45][59]. It was obtained by oxidation of di-tert-butyl ketoxime (1f) with silver(I) oxide (Ag2O) in benzene at 25 °C (Scheme 2). This radical

• is stable at 25 °C in n-hexane. In pure form it is storable only at −78 °C as a solid. At room temperature, radical 8 is a blue oil. When storing 8 in the dark without solvent at 25 °C for a week, the following decomposition products were identified: di-tert-butyl ketone (9, 42%), di-tert-butyl

Photocatalysis with organic dyes: facile access to reactive intermediates for synthesis

• Stephanie G. E. Amos,
• Marion Garreau,
• Luca Buzzetti and
• Jerome Waser

Beilstein J. Org. Chem. 2020, 16, 1163–1187, doi:10.3762/bjoc.16.103

• the peroxo radical III when using O2. Nicewicz and co-workers noticed that the presence of nucleophilic peroxide radicals generated from O2 led to the degradation of the classical Mes-Acr+ photocatalyst. The presence of bulky tert-butyl groups in the 3- and 6-positions provided a greater catalyst

• , including eosin Y (OD13) [163] and acridine red [164]. Wang and co-workers relied on this approach for the development of an organophotocatalytic vinylation of tetrahydrofuran derivatives with alkynes (Scheme 40) [165]. In this method, the photoexcited OD13 induces the cleavage of the weak O–O bond of tert

• -butyl peroxide (40.1), generating a hydroxy radical and a tert-butoxy radical. The latter promotes an H abstraction from the substrate tetrahydrofuran (8.1), giving access to an α-oxy C(sp3) radical, which is trapped by an alkyne 40.2, providing the desired vinylation product 40.3. Sulfur-centered

Synthesis and properties of quinazoline-based versatile exciplex-forming compounds

• Rasa Keruckiene,
• Simona Vekteryte,
• Ervinas Urbonas,
• Matas Guzauskas,
• Eigirdas Skuodis,
• Dmytro Volyniuk and
• Juozas V. Grazulevicius

Beilstein J. Org. Chem. 2020, 16, 1142–1153, doi:10.3762/bjoc.16.101

• carbazole, phenothiazine, and 2,7-di-tert-butyl-9,9-dimethylacridine donor moieties on the electron-releasing energy. The phenothiazine-substituted quinazoline compound 3 required the lowest energy for electron release compared to the other compounds studied. The electron affinity values were comparable as

• procedure reported in literature [27]. OLED fabrication and characterization was carried out according to the procedure reported earlier [28]. Materials 2-Aminobenzophenone, 3,5-difluorobenzaldehyde, ammonium acetate, phenothiazine, sodium hydride, sodium sulfate, tert-butyl chloride, zinc chloride

• (purchased from Aldrich), 9H-carbazole, copper(II) chloride (purchased from Reakhim), and 2,7-di-tert-butyl-9,9-dimethyl-9,10-dihydroacridine (purchased from Center for Physical Sciences and Technology) were used as received. Thin-layer chromatography was performed using TLC plates covered with silica gel

Fluorinated phenylalanines: synthesis and pharmaceutical applications

• Laila F. Awad and
• Mohammed Salah Ayoup

Beilstein J. Org. Chem. 2020, 16, 1022–1050, doi:10.3762/bjoc.16.91

• methyl ester performed better than the ethyl ester (74% versus 60% yield). However, N-protecting groups such as Boc, Fmoc, and Cbz were not compatible with the fluorination (0–10% yield). Moreover, when tert-butyl, trityl, and adamantyl protecting groups were installed for C-terminal protection

Pd-catalyzed asymmetric Suzuki–Miyaura coupling reactions for the synthesis of chiral biaryl compounds with a large steric substituent at the 2-position

• Yongsu Li,
• Bendu Pan,
• Xuefeng He,
• Wang Xia,
• Yaqi Zhang,
• Hao Liang,
• Chitreddy V. Subba Reddy,
• Rihui Cao and
• Liqin Qiu

Beilstein J. Org. Chem. 2020, 16, 966–973, doi:10.3762/bjoc.16.85

• enantioselectivity. However, with the substitution of an ester group for the amino moiety, interestingly, the situation changed significantly. The greater the ester substituent, the better the reaction results including the product yield and ee value. When the functional group changed from methyl ester to tert-butyl