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

• more efficient but also more toxic HMPA. A few modifications made in the original procedure in combination with column chromatography led to pure product 2 in good yield (Scheme 2). With azide precursor 2 in hand as an aldehyde component, the Ugi reaction was performed with various isocyanides 4

• , amines 5, and phenylpropargylic acid (3a) or propargylic acid (3b, Scheme 3). In most cases, the reactions were carried under standard conditions for Ugi-4CR mentioned in the literature. Aldehyde and amine were premixed for 2 hours in methanol, then acid and isocyanide were sequentially added. Stirring

[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

• with tosylhydrazone The first publication on the synthesis of methanofullerenes via tosyl derivatives appeared in 1993 [83]. According to the original source, C60 cyclopropanation is assumed to involve a diazo compound preliminarily synthesized from an aldehyde- or ketone-based tosylhydrazone. The

• reported [160]. In a study by Kumar and co-workers [161], the synthesis of methanofullerenes 206 and 207 was based on 3-methoxy-4-hydroxycinnamic aldehyde and a chalcon obtained by Claison condensation of acetophenone with 2-hydroxy-5-nitrobenzaldehyde (Scheme 41). Further, the same team obtained

• methanofullerene adduct 208 based on 2-nitrocinnamic aldehyde (Scheme 42) [116]. Hummelen and co-workers [131] worked on creating derivatives of H-bound fullerene associates. For instance, methyl 5-oxo-5-(3,4-bishexyloxy)phenylpentanoate was converted via a tosyl derivative to a methanofullerene derivative of

Menthyl esterification allows chiral resolution for the synthesis of artificial glutamate analogs

• Kenji Morokuma,
• Shuntaro Tsukamoto,
• Kyosuke Mori,
• Kei Miyako,
• Ryuichi Sakai,
• Raku Irie and
• Masato Oikawa

Beilstein J. Org. Chem. 2021, 17, 540–550, doi:10.3762/bjoc.17.48

• (rac)-16 (87% yield), followed by alkaline methanolysis (74% yield) [17] and Pinnick oxidation (43% yield) [18][19][20], delivered carboxylic acid (rac)-19. Unfortunately, an attempt to improve the oxidation yield was not fruitful; the oxidation of aldehyde (rac)-18 with TEMPO [21] resulted in a lower

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

• solvent (DMF, MeCN, ethyl acetate, DMSO, solvent free) on the activity and selectivity of the nanocatalysts has been noted [27][41][42][43][44]. Furthermore, all the reported methodologies use either molecular oxygen together with an aldehyde as a co-reductant, or only a “green” peroxide (H2O2, TBHP) as

Progress in the total synthesis of inthomycins

• Bidyut Kumar Senapati

Beilstein J. Org. Chem. 2021, 17, 58–82, doi:10.3762/bjoc.17.7

• oxidation of (Z)-15a followed by immediate aldol condensation afforded racemic phenol ester (rac)-17 via aldehyde 16. However, several attempts to form enantioenriched aldol fragment 18 using both a chiral auxiliary [25][26][27][28] and catalytic asymmetric [29][30] procedures proceeded without success

• bromine in acetic acid, and then triethyl phosphite. Next, compound 28 was treated with sodium hydride followed by aldehyde 29 [37] to give (E,E)-dienyl stannane 30 in 50% yield. The key Stille coupling between 30 and vinyl iodide 31, prepared by Takai reaction [38] of phenylacetaldehyde, in presence of

• mixture of (Z,E)/(E,E)-36a, respectively). Aldehyde 35 was then converted into dibromide 37 using PPh3/CBr4 followed by stereoselective palladium-catalyzed monoreduction according to the literature available protocol [41] to give vinyl bromide 38 in 76% yield (Z/E as 99:1 mixture). Iodide 15a [42] was

Recent progress in the synthesis of homotropane alkaloids adaline, euphococcinine and N-methyleuphococcinine

• Dimas J. P. Lima,
• Antonio E. G. Santana,
• Michael A. Birkett and
• Ricardo S. Porto

Beilstein J. Org. Chem. 2021, 17, 28–41, doi:10.3762/bjoc.17.4

• LiH2NBH3 in THF at 40 °C to provide amino alcohol (−)-44 in 88% yield. This amino alcohol underwent cyclization through a one-pot process in the presence of TPAP-NMO, which involved oxidation in generated aldehyde 45, followed by dehydrocondensation leading to N,O-tricyclic acetal (−)-46 in 80% yield

• in a 9:1 ratio. After chromatographic separation, alcohol (−)-77a, isolated in 67% yield and >99% de was subjected to a Claisen rearrangement, leading to aldehyde (−)-78 in 79% yield (96% de determined by 1H NMR). (−)-78 was treated with vinylmagnesium bromide to give a mixture of allyl alcohols

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

• heteroaromatic aldehyde 2-pyridinecarbaldehyde (2q) gave the respective dehydrated product 4q in 96% yield, whereas 2-thiophene (2r) resulted in the desired product 3r but in a low yield (Table 2, entries 17 and 18). Subsequently, several azaarenes in combination with 4-nitrobenzaldehyde (2a) were also evaluated

• -nitrobenzaldehyde (2a). Plausible mechanism for the formation of 2-(6-methylpyridin-2-yl)-1-(4-nitrophenyl)ethan-1-ol (3a) under standard reaction conditions from 2,6-dimethylpyridine (1a) and 4-nitrobenzaldehyde (2a). Optimization of the reaction conditions.a Variation of the aldehyde component 2.a Variation of

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

• triquinane (±)-hirsutene (14) [24] (Scheme 1D). In 2011, the same research group used allenyl diazo compound 38, which was generated from the reaction between aldehyde 37 and p-toluenesulfonehydrazide in the presence of sodium hydride upon heating, to produce diyl 40 [29] (Scheme 2A). The intramolecular

• upon refluxing in toluene and subsequent epoxidation afforded 51 [32], which was converted to (−)-crinipelline A (15) in two steps. The synthesis of waihoensene (16) commenced with the conversion of aldehyde 52a to the corresponding hydrazone 52b, which was treated with sodium hydride under reflux to

• underwent successive intramolecular Michael addition and hydrolytic nitrile reduction to give 79 in 46% yield in two steps. Extensive studies of the nitrile reduction eventually identified that Et3Al and DIBAL-H could effectively reduce the nitrile group to the corresponding aldehyde and treatment with

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

• aromatization to produce 5a. KI may play a key role in the last step, and we suspected that it can promote the removal of bromide. Although 5a can theoretically be synthesized through a three-component reaction of 1b, 2a, and an appropriate aldehyde, for example, acetaldehyde [50][51] owing to the insufficient

A novel and robust heterogeneous Cu catalyst using modified lignosulfonate as support for the synthesis of nitrogen-containing heterocycles

• Bingbing Lai,
• Meng Ye,
• Ping Liu,
• Minghao Li,
• Rongxian Bai and
• Yanlong Gu

Beilstein J. Org. Chem. 2020, 16, 2888–2902, doi:10.3762/bjoc.16.238

• needed. In this work, we present a novel heterogeneous Cu catalyst using modified LS as support by a consecutive process involving the phenol–aldehyde condensation of LS with 2-formylbenzenesulfonic acid sodium (FAS), ion exchange and acidification. Special interest is given in the application of the

• , the support was prepared through phenol–formaldehyde condensation reaction of LS and FAS. The FAS was chosen to embellish LS in consideration of the following reason: FAS skeleton consists of both aldehyde and sulfonic groups, so the grafting of FAS and LS can be easily realized via phenol

• successfully prepared through immobilizing Cu on a novel and ecofriendly supporting material synthesized by the phenyl–aldehyde condensation reaction of FAS and LS. This catalyst could be used for the synthesis of several nitrogen-containing heterocycles and exhibited excellent catalytic activity. ICP-MS data

One-pot multicomponent green Hantzsch synthesis of 1,2-dihydropyridine derivatives with antiproliferative activity

• Giovanna Bosica,
• Kaylie Demanuele,
• José M. Padrón and
• Adrián Puerta

Beilstein J. Org. Chem. 2020, 16, 2862–2869, doi:10.3762/bjoc.16.235

• was dried overnight at 110 °C and ultimately calcined at 250 °C in a furnace under air for 4 h to obtain a white powder (1 g), which was stored in a calcium chloride/silica-filled desiccator. General method The general method involved the addition of 1 equiv of the aldehyde (5 mmol), 2 equiv ethyl

Using multiple self-sorting for switching functions in discrete multicomponent systems

• Amit Ghosh and
• Michael Schmittel

Beilstein J. Org. Chem. 2020, 16, 2831–2853, doi:10.3762/bjoc.16.233

• )] (Figure 4e). Equally, Schalley and Nitschke developed a guest-induced self-sorting based on two new Zn4L6 cages (Figure 5a) using the aldehyde 9 and the diamine subcomponents 7 and 8 that contained either the naphthalene diimide or zinc porphyrin moiety [51]. Both cages respond selectively to distinct

• self-assembly of the triamines 10 and 11 in the presence of the aldehyde 12 and cobalt(II) ions [52]. When all components were mixed in a single reaction vessel, the 1H NMR spectrum indicated the formation of homoleptic as well as heteroleptic species. In the following, they explored the ability of the

3-Acetoxy-fatty acid isoprenyl esters from androconia of the ithomiine butterfly Ithomia salapia

• Florian Mann,
• Daiane Szczerbowski,
• Lisa de Silva,
• Melanie McClure,
• Marianne Elias and
• Stefan Schulz

Beilstein J. Org. Chem. 2020, 16, 2776–2787, doi:10.3762/bjoc.16.228

• o-iodoxybenzoic acid (IBX) [31]. The resulting aldehyde was transformed into β-ketoacid 16 with ethyl diaazoacetate and SnCl2 [32], which upon reduction with NaBH4 in methanol delivered methyl 3-hydroxyoctadecanoate (17). Transesterification was performed with 3-methyl-3-buten-1-ol using distannoxan

Selective and reversible 1,3-dipolar cycloaddition of 6-aryl-1,5-diazabicyclo[3.1.0]hexanes with 1,3-diphenylprop-2-en-1-ones under microwave irradiation

• Alexander P. Molchanov,
• Mariia M. Efremova,
• Mariya A. Kryukova and
• Mikhail A. Kuznetsov

Beilstein J. Org. Chem. 2020, 16, 2679–2686, doi:10.3762/bjoc.16.218

• liberation of the aromatic aldehyde and formation of the new azomethine imines. Conclusion The cycloaddition of azomethine imines, generated from 6-aryl-1,5-diazabicyclo[3.1.0]hexanes under microwave heating, with 1,3-diarylpropenones occurs regioselective with the formation of 2-benzoyl-substituted pyrazolo

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

• molecules 1f–j (Figure 1) were synthesized by a modular approach described by Heitmann et al. [15]. The boronic ester 22 was prepared according to a mixed aldehyde procedure [16][17] and the substituted azopyridines 14, 18, 20, and 21 were attached using Suzuki conditions. Synthesis of azopyridines 10–12

Palladium nanoparticles supported on chitin-based nanomaterials as heterogeneous catalysts for the Heck coupling reaction

• Tony Jin,
• Malickah Hicks,
• Davis Kurdyla,
• Sabahudin Hrapovic,
• Edmond Lam and
• Audrey Moores

Beilstein J. Org. Chem. 2020, 16, 2477–2483, doi:10.3762/bjoc.16.201

• and aldehyde–amine–alkyne (A3) coupling reactions [16]. Off this discovery, in this letter, we further expand the scope of using both ChNCs and ChsNCs as a catalyst support for Pd NPs to allow access towards other highly relevant C–C bond-forming reactions. A one-pot fabrication method is used to

Recent developments in enantioselective photocatalysis

• Callum Prentice,
• James Morrisson,
• Andrew D. Smith and
• Eli Zysman-Colman

Beilstein J. Org. Chem. 2020, 16, 2363–2441, doi:10.3762/bjoc.16.197

•  46) [112]. The proposed mechanism involves a reductive quenching cycle using TEEDA as a sacrificial reductant to generate [Ru]•−. Simultaneously the chiral Lewis acid catalyst forms complex 286 with both starting materials. [Ru]•− then reduces the activated aldehyde to give ketyl radical anion 286

Chan–Evans–Lam N1-(het)arylation and N1-alkеnylation of 4-fluoroalkylpyrimidin-2(1H)-ones

• Viktor M. Tkachuk,
• Oleh O. Lukianov,
• Mykhailo V. Vovk,
• Isabelle Gillaizeau and
• Volodymyr A. Sukach

Beilstein J. Org. Chem. 2020, 16, 2304–2313, doi:10.3762/bjoc.16.191

• ,n in moderate to satisfactory yields of 43–60%. It is notable that in our case, the Chan–Evans–Lam arylation is tolerant to many sensitive functional groups contained in boronic acids, thereby providing a synthetic entry to products 3 with the aldehyde (in compound 3k), phenolic meta- and para

• -hydroxy (3l,m), and hydroxymethyl (3n) substituents. At the same time, the reaction with para-N,N-dimethylaminomethylphenylboronic acid failed to produce the desired arylated product due to the oxidation of the substituent to the aldehyde group and, probably, some other related side processes. As might be

Styryl-based new organic chromophores bearing free amino and azomethine groups: synthesis, photophysical, NLO, and thermal properties

• Anka Utama Putra,
• Deniz Çakmaz,
• Nurgül Seferoğlu,
• Alberto Barsella and
• Zeynel Seferoğlu

Beilstein J. Org. Chem. 2020, 16, 2282–2296, doi:10.3762/bjoc.16.189

• having a free amino and strong donor-acceptor groups and a pyridin-2-yl moiety were synthesized by the base-catalyzed condensation of 2 with different aldehyde derivatives in ethanol, as depicted in Scheme 1. Further reactions of the dyes 3–7 with salicylaldehyde under basic conditions resulted in 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

Azo-dimethylaminopyridine-functionalized Ni(II)-porphyrin as a photoswitchable nucleophilic catalyst

• Jannis Ludwig,
• Julian Helberg,
• Hendrik Zipse and
• Rainer Herges

Beilstein J. Org. Chem. 2020, 16, 2119–2126, doi:10.3762/bjoc.16.179

• modular approach described by Heitmann et al. was chosen [30] since the alternative mixed aldehyde route failed for related porphyrin derivatives [17]. Ni-porphyrin precursor 3 and 4-(N,N-dimethylaminoazo)pyridine 4 were synthesized according to literature procedures [17][30]. Following the conditions for

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

• -azirine, an efficient source of nitrogen, was employed as starting material for the synthesis of oxazole with various coupling partners such as aldehyde, trifluoroacetic acid, etc. [8][45][46][47][48][49][50] (Scheme 1). Thiazole is a common structural motif that is found in a wide variety of naturally

Convenient access to pyrrolidin-3-ylphosphonic acids and tetrahydro-2H-pyran-3-ylphosphonates with multiple contiguous stereocenters from nonracemic adducts of a Ni(II)-catalyzed Michael reaction

• Alexander N. Reznikov,
• Dmitry S. Nikerov,
• Anastasiya E. Sibiryakova,
• Victor B. Rybakov,
• Evgeniy V. Golovin and
• Yuri N. Klimochkin

Beilstein J. Org. Chem. 2020, 16, 2073–2079, doi:10.3762/bjoc.16.174

• carbonyl leads to a mixture of unidentified products. At the next stage of this work, the Henry/acetalization reaction with phosphonate 6e was studied. To optimize the reaction conditions various bases and solvents were used. The reaction of phosphonate 6e with propionic aldehyde 12a was used as a model

Syntheses of spliceostatins and thailanstatins: a review

• William A. Donaldson

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

• Syntheses from ʟ-threonine-derived aldehyde Three groups utilized 4-formyl-2,2,5-trimethyl-3-oxazolidine (24) [21], derived from relatively inexpensive ʟ-threonine (<$1/g in bulk) as a chiral pool precursor for the amine stereocenter of the (all-cis)-2,3,5,6-tetrasubstituted tetrahydropyran fragment. In

• with a poor stereoselectivity, however, a similar reduction of the diethyl acetal of 38, followed by an acetal hydrolysis gave the aldehyde 39 with a good stereocontrol (>10:1). It is not possible to make a direct comparison of the efficiency of these three routes as they do not lead to an identical

• strategies that rely on the generation of the C-14 stereocenter by stereoselective C–N bond formation. The Jacobsen group utilized an asymmetric Cr(III)-catalyzed cycloaddition reaction [27] between (2Z,4E)-3-(triethylsilyloxy)-2,4-hexadiene (40) and the aldehyde 41 to generate the 4-silyloxydihydropyran 43

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

• bond of 1 to generate a new carbon-centered radical II, with sequential attack on the aldehyde group. The oxygen radical III thus formed undergoes a formal 1,2-H shift to generate the benzyl radical IV [45][46]. Finally, hydrogen abstraction by the sulfate radical anion (SO4•−) from the benzyl radical