Synthesis of new bile acid-fused tetrazoles using the Schmidt reaction

• Dušan Đ. Škorić,
• Olivera R. Klisurić,
• Dimitar S. Jakimov,
• Marija N. Sakač and
• János J. Csanádi

Beilstein J. Org. Chem. 2021, 17, 2611–2620, doi:10.3762/bjoc.17.174

• selective acetylation [43], followed by oxidation. Enones 4 and 8 were prepared by dehydrogenation of corresponding ketones with SeO2 in refluxing acetic acid [44]. Microwave-assisted heating of the reaction mixture in a closed vessel (150 °C) helped in decreasing the reaction time for dehydrogenation

• acid, reflux, 12 h (74% for 4; 69% for 8); d) SeO2, acetic acid, microwave irradiation, 150 °C, 15 min (74% for 4; 67% for 8); and e) Ac2O, benzene/pyridine, rt, 24 h (74%). Synthesis of 7-oxo intermediate 11 from chenodeoxycholic acid (9). Reagents and conditions: a) EtOAc, pTsOH, reflux, 12 h (66

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

• , underwent cyclization in the presence of silica gel to give ethyl 6-(hetero)aryl-2,3-dihydro-1H-pyrrolizine-5-carboxylates within minutes upon microwave heating in xylene at 150 °C. Instead of functioning as a nucleophile, the enaminone acted as an electrophile at its carbonyl group during the cyclization

• . Yields of the bicyclic products were generally above 75%. The analogous microwave-assisted reaction to produce ethyl 2-aryl-5,6,7,8-tetrahydroindolizine-3-carboxylates from (E)-ethyl 2-[2-(2-oxo-2-arylethylidene)piperidin-1-yl]acetates failed in nonpolar solvents, but occurred in ethanol at lower

• temperature and microwave power, although requiring much longer time. A possible mechanism for the cyclization is presented, and further functionalization of the newly created pyrrole ring in the dihydropyrrolizine core is described. Keywords: dihydropyrrolizines; enaminones; microwaves; silica gel

(Phenylamino)pyrimidine-1,2,3-triazole derivatives as analogs of imatinib: searching for novel compounds against chronic myeloid leukemia

• Luiz Claudio Ferreira Pimentel,
• Lucas Villas Boas Hoelz,
• Henayle Fernandes Canzian,
• Frederico Silva Castelo Branco,
• Andressa Paula de Oliveira,
• Vinicius Rangel Campos,
• Floriano Paes Silva Júnior,
• Rafael Ferreira Dantas,
• Jackson Antônio Lamounier Camargos Resende,
• Anna Claudia Cunha,
• Nubia Boechat and
• Mônica Macedo Bastos

Beilstein J. Org. Chem. 2021, 17, 2260–2269, doi:10.3762/bjoc.17.144

• )pyrimidine-pyridine (PAPP) group as a pharmacophoric fragment, and these compounds were biologically evaluated. The synthesis of twelve new compounds was performed in three steps and assisted by microwave irradiation in a 1,3-dipolar cycloaddition to obtain 1,2,3-triazole derivatives substituted on carbon C

• cycloaddition reactions via the copper-catalyzed 1,3-dipolar cycloaddition reaction (CuAAC) of the azides 5 and 9 with suitably functionalized acetylenes 6a–j, using sodium ascorbate and copper sulfate in ACN/H2O 2:1 under microwave irradiation were carried out to obtain the 1,4-regioisomers of the final

Recent advances in the syntheses of anthracene derivatives

• Giovanni S. Baviera and
• Paulo M. Donate

Beilstein J. Org. Chem. 2021, 17, 2028–2050, doi:10.3762/bjoc.17.131

• ]. The direct synthesis of anthracene derivatives is rare and most methods usually involve more than one reaction step. For example, in 2008, Deiters and co-workers described an efficient two-step route to prepare substituted anthracenes and azaanthracenes via microwave-assisted [2 + 2 + 2

• expected products [76]. Sun and co-workers modified the method proposed by Singh. In 2011, they reported a method that employed molecular iodine as the catalyst, under microwave radiation as heat source, and obtained tetrahydrobenzo[a]xanthene-11-one and diazabenzo[a]anthracene-9,11-dione derivatives in

• good to excellent yields (70–94%) [77]. Then, in 2012, Sun and co-workers reported another method employing molecular iodine as catalyst under reflux with acetic acid instead of microwave radiation and also obtained good yields (66–89%) [78]. Because the three methodologies provided good yields, 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

• decomposition of N-pyridylbenzotriazoles. Later, the reaction conditions were modified to make this reaction more versatile and operationally simple such as by the use of microwave irradiation [12]. Meanwhile, the Fischer indole synthesis was successfully extended for the synthesis of significant biologically

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

• alkyne 155 was reacted with bromobenzene and sodium azide under microwave heating in an EtOH/H2O mixture in the presence of copper iodide, sodium ascorbate, and N,N-dimethylethylenediamine (156) to afford the double-headed nucleoside 157a. The reaction of the terminal alkyne 155 with benzyl bromide and

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

• stimulation by application of variable temperature zones, light or microwave irradiation, electrolysis and even high frequency sonication. The ability to quickly and easily assemble and modify a flow setup allows not only the chemical reaction to be performed as a continuous dynamic flow process but also for

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

• microwave stimulations [18][19][20][21][22][23][24][25][26]. Recently, visible light photoredox catalysis has emerged as a powerful and environment-friendly method in organic synthesis by activating organic molecules under mild reaction conditions [27][28]. In this context, the Li and Cai groups

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

• was the only effective reagent when performing the reaction at 60 °C in THF [16]. Ketimines were also synthesized with Ti(OEt)4, under microwave irradiation in a solvent-free system [20]. In hindered ketones, Ti(OiPr)4 or Ti(OEt)4 using vacuum or under a nitrogen flow were effective to tert

Synthesis of multiply fluorinated N-acetyl-D-glucosamine and D-galactosamine analogs via the corresponding deoxyfluorinated glucosazide and galactosazide phenyl thioglycosides

• Vojtěch Hamala,
• Lucie Červenková Šťastná,
• Martin Kurfiřt,
• Petra Cuřínová,
• Martin Dračínský and
• Jindřich Karban

Beilstein J. Org. Chem. 2021, 17, 1086–1095, doi:10.3762/bjoc.17.85

• reaction with diethylamino sulfurtrifluoride (DAST) [27]. This reaction was greatly improved by microwave irradiation, especially in the GalNAc series [31][32]. The deoxyfluorination of the secondary hydroxy groups at the 3- and 4-positions was accomplished using a treatment of the C3/4 hydroxy groups with

• sulfurtrifluoride (DAST) [51], but our experiments revealed that DAST-mediated C6-deoxyfluorination of thioglycosides 14–17 and 19 proceeded satisfactorily under microwave irradiation, on condition that pure or substantially enriched α-anomers were subjected to reaction with DAST, yielding thioglycosides 22–26

Recent advances in palladium-catalysed asymmetric 1,4–additions of arylboronic acids to conjugated enones and chromones

• Jan Bartáček,
• Jan Svoboda,
• Martin Kocúrik,
• Jaroslav Pochobradský,
• Alexander Čegan,
• Miloš Sedlák and
• Jiří Váňa

Beilstein J. Org. Chem. 2021, 17, 1048–1085, doi:10.3762/bjoc.17.84

• the reaction (Scheme 6) [40]. A different approach using microwave irradiation was explored by the group of Toma et al. [41]. After an initial tuning of the reaction conditions of a catalytic system based on Pd(OAc)2/2,2’-bipy several optically pure phosphoramidite and diphosphine ligands in

• organoboron reagents to enones [3][26][35]. Enantioselective β-arylation of cyclohexanone [38]. Application of L2/Pd(OAc)2 in the total synthesis of terpenes [8]. Plausible catalytic cycle for the addition of phenylboronic acid to 2-cyclohexenone catalysed by L3/Pd(dba)2 [40]. Microwave-assisted addition of

Synthetic accesses to biguanide compounds

• Oleksandr Grytsai,
• Cyril Ronco and
• Rachid Benhida

Beilstein J. Org. Chem. 2021, 17, 1001–1040, doi:10.3762/bjoc.17.82

• procedure reported by Cohn have been attempted to increase the yields of the biguanide products. In particular, microwave-assisted reactions for the synthesis of biguanides have received growing attention. The conditions applied usually comprised the use of 1 equivalent of hydrochloric acid in a polar

• aprotic solvent, which led to moderate to good conversions after less than 30 minutes. Chen et al. were the first to show a significant acceleration of the reaction between cyanoguanidine and variously substituted aniline hydrochlorides under microwave irradiation (Scheme 7A) [22]. The reaction was

• the cyanoguanidine reactivity by preventing proton exchanges, trimethylsilyl chloride was used in combination with microwave (MW) activation. Using acetonitrile and MW irradiation at 150 °C as the best conditions, Mayer et al. successfully prepared various N1-mono- and N1,N1-disubstituted aryl- and

Prins cyclization-mediated stereoselective synthesis of tetrahydropyrans and dihydropyrans: an inspection of twenty years

• Asha Budakoti,
• Pradip Kumar Mondal,
• Prachi Verma and
• Jagadish Khamrai

Beilstein J. Org. Chem. 2021, 17, 932–963, doi:10.3762/bjoc.17.77

• ]. A strategy involving BiCl3-catalyzed microwave-assisted Prins cyclization of homoallylic alcohol 101 with an aldehyde 102 was successfully employed for the synthesis of 4-chloro-cis-2,6-disubstituted tetrahydropyran 103 as a single diastereomer [57], as shown in Scheme 23. In continuation, 4

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

• Shivani Gulati Stephy Elza John Nagula Shankaraiah Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad 500 037, India 10.3762/bjoc.17.71 Abstract Microwave-assisted (MWA) multicomponent reactions (MCRs) have successfully emerged as one

• enhanced yield and efficiency with microwave assistance. The highlights of MWA-MCRs are high yields, reduced reaction time, selectivity, atom economy and simpler purification techniques, such an approach can accelerate the drug discovery process. The present review focuses on the recent advances in MWA

• -MCRs and their mechanistic insights over the past decade and shed light on its advantage over the conventional approach. Keywords: cycloaddition; Knoevenagel condensation; Michael addition; microwave; multicomponent reactions; Introduction Recently, organic chemists are focussed to develop

Synthesis of dibenzosuberenone-based novel polycyclic π-conjugated dihydropyridazines, pyridazines and pyrroles

• Ramazan Koçak and
• Arif Daştan

Beilstein J. Org. Chem. 2021, 17, 719–729, doi:10.3762/bjoc.17.61

• unsubstituted pyrrole 10ac was synthesized by the reaction of pyrrole 10ab with 4 equivalents of KOH under microwave irradiation (Scheme 6). The reaction of 2-pyridylpyridazine 4b with Zn did not work at room temperature. Under reflux conditions compound 10ba was obtained, which contained the corresponding

α,γ-Dioxygenated amides via tandem Brook rearrangement/radical oxygenation reactions and their application to syntheses of γ-lactams

• Mikhail K. Klychnikov,
• Radek Pohl,
• Ivana Císařová and
• Ullrich Jahn

Beilstein J. Org. Chem. 2021, 17, 688–704, doi:10.3762/bjoc.17.58

• α-(aminoxy)amides 9. Thermal radical cyclization of compounds 9 and further deprotection (general procedure) The α-(aminoxy)amide 9 (0.65 mmol) was heated in t-BuOH (6 mL) in a microwave reactor at 150 °C for 1 h. The reaction mixture was diluted with diethyl ether (5 mL), transferred into a round

Effective microwave-assisted approach to 1,2,3-triazolobenzodiazepinones via tandem Ugi reaction/catalyst-free intramolecular azide–alkyne cycloaddition

• Maryna O. Mazur,
• Oleksii S. Zhelavskyi,
• Eugene M. Zviagin,
• Svitlana V. Shishkina,
• Vladimir I. Musatov,
• Maksim A. Kolosov,
• Elena H. Shvets,
• Anna Yu. Andryushchenko and
• Valentyn A. Chebanov

Beilstein J. Org. Chem. 2021, 17, 678–687, doi:10.3762/bjoc.17.57

• followed by microwave-assisted intramolecular azide–alkyne cycloaddition (IAAC) gave a series of target heterocyclic compounds in moderate to excellent yields. Surprisingly, the normally required ruthenium-based catalysts were found to not affect the IAAC, only making isolation of the target compounds

• harder while the microwave-assisted catalyst-free conditions were effective for both terminal and non-terminal alkynes. Keywords: click chemistry; microwave chemistry; multicomponent reactions; triazolobenzodiazepines; Ugi reaction; Introduction Benzannulated heterocycles are among the most important

• temperature conditions for the cyclization, performing a reaction under microwave irradiation in a sealed vial, and changed the solvent to less toxic (than benzene) toluene. That led to a decreasing reaction time to 1–1.5 hours (the reaction progress was monitored by TLC) with no impact on the product purity

Valorisation of plastic waste via metal-catalysed depolymerisation

• Francesca Liguori,
• Carmen Moreno-Marrodán and
• Pierluigi Barbaro

Beilstein J. Org. Chem. 2021, 17, 589–621, doi:10.3762/bjoc.17.53

• , glycolysis of PET was performed under microwave heating in the presence of Zn(OAc)2, yielding BHET with an 80% selectivity at 97% conversion due to formation of dimers (Table 2, entry 7) [203][204]. Soluble metal chlorides (zinc, magnesium, iron, zirconium, cobalt, nickel) were also explored as catalysts in

• metal (complex) catalysts, methanolysis of PLA was recently described using alkali metal halides [271]. In an optimised experiment, PLA from various goods (cups, fork, spoons, containers, Mw 120000–260000 g⋅mol−1) was converted into Me-La in up to 97% yield using 2.5 mol % KF, 180 °C microwave heating

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

• microwave irradiation, a mixture of monoacylated and diacylated products 3 and 4 in 52% and 33% yield, respectively, was isolated [28]. Enzymatic hydroxylation 3-Ketosteroid 9α-hydroxylase (KSH) from R. rhodochrous has been shown to oxidize C9 in several steroids [29]. This enzyme consists of two

• p-toluenesulfonic acid monohydrate (2.8 mg, 0,008 mmol, 0,01 equiv) in a beaker was subjected to continuous mode of microwave irradiation (800 W) at high power setting in a domestic microwave oven for 6 min. After this, the mixture was cooled to room temperature, and saturated aqueous NaHCO3 (5 mL

Synthesis of N-perfluoroalkyl-3,4-disubstituted pyrroles by rhodium-catalyzed transannulation of N-fluoroalkyl-1,2,3-triazoles with terminal alkynes

• Olga Bakhanovich,
• Viktor Khutorianskyi,
• Vladimir Motornov and
• Petr Beier

Beilstein J. Org. Chem. 2021, 17, 504–510, doi:10.3762/bjoc.17.44

• Prague, Czech Republic 10.3762/bjoc.17.44 Abstract The rhodium-catalyzed transannulation of N-perfluoroalkyl-1,2,3-triazoles with aromatic and aliphatic terminal alkynes under microwave heating conditions afforded N-perfluoroalkyl-3,4-disubstituted pyrroles (major products) and N-fluoroalkyl-2,4

Diels–Alder reaction of β-fluoro-β-nitrostyrenes with cyclic dienes

• Savva A. Ponomarev,
• Roman V. Larkovich,
• Alexander S. Aldoshin,
• Andrey A. Tabolin,
• Sema L. Ioffe,
• Jonathan Groß,
• Till Opatz and
• Valentine G. Nenajdenko

Beilstein J. Org. Chem. 2021, 17, 283–292, doi:10.3762/bjoc.17.27

• = 56:44) was observed for the product 2m. Next, the reaction with 1,3-cyclohexadiene (CHD) was investigated. It was found that the reaction is very sensitive to the structure of starting diene and in the case of CHD proceeds much more slowly. Both thermal and microwave (MW) activation (Scheme 3) was

• °C) and CHD at 110 °C. Scope of the nitrostyrenes 1 in the Diels–Alder reaction with CPD (dr = exo:endo). The Diels–Alder reaction of nitrostyrene 1h with spiro[2.4]hepta-4,6-diene. Diels–Alder reaction of nitrostyrenes 1 with CHD (dr = exo:endo). (а) Reaction under microwave activation. Kinetic

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

• addition, another modification was made in order to increase the speed of the reaction of sodium halodifluoroacetate and alkenes. This was achieved by the use of microwave irradiation in THF solution, which allowed the reactions to be completed within 5 minutes [31]. An application of this method to

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

• development of this topic [8][9][10][11]. On the contrary, only a few examples can be found in the literature where a phosphorus-containing substituent is directly attached to the purine ring [12][13]. In 2008, an SNAr–Arbuzov reaction was developed for 6-chloropurine derivatives under microwave irradiation

• : DMSO-d6, 90 °C. Single-crystal X-ray analysis of diethyl (9-heptyl-2-(4-phenyl-1H-1,2,3-triazol-1-yl)-9H-purin-6-yl)phosphonate (4d). CCDC-2044976. Structural diversity and synthetic methods of purinylphosphonates. MWI = microwave irradiation; LG = leaving group. Synthetic routes for the formation of

An atom-economical addition of methyl azaarenes with aromatic aldehydes via benzylic C(sp³)–H bond functionalization under solvent- and catalyst-free conditions

• Divya Rohini Yennamaneni,
• Vasu Amrutham,
• Krishna Sai Gajula,
• Rammurthy Banothu,
• Murali Boosa and
• Narender Nama

Beilstein J. Org. Chem. 2020, 16, 3093–3103, doi:10.3762/bjoc.16.259

• times [30]. Rao et al. performed similar reactions without catalyst under microwave irradiation in the presence of water as a solvent [31], but when considering an industrial scale, there are numerous factors that serves as obstacles for the usage of microwave reactors, such as escalated heat loss

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

• -unsaturated enone to afford conidiogenone B (171) in 32% yield upon treatment with RhCl3 in microwave. The reaction mechanism of Danheiser’s [3 + 2] annulation is shown according to the Danheiser’s proposal [74] (Scheme 13C, inset). Initial complexation of the α,β-unsaturated ketone 167 and titanium