Facile access to 3-sulfonylquinolines via Knoevenagel condensation/aza-Wittig reaction cascade involving ortho-azidobenzaldehydes and β-ketosulfonamides and sulfones

• Ksenia Malkova,
• Andrey Bubyrev,
• Stanislav Kalinin and
• Dmitry Dar’in

Beilstein J. Org. Chem. 2023, 19, 800–807, doi:10.3762/bjoc.19.60

• through a range of synthetic methodologies suggested recently. Cyclization strategies [35][36][37][38][39][40][41][42][43][44][45] as well as cycloaddition/cyclocondensation techniques [46][47][48][49][50][51] represent those with hetero-ring construction. Alternative approaches rely on a peripheral

Sulfate radical anion-induced benzylic oxidation of N-(arylsulfonyl)benzylamines to N-arylsulfonylimines

• Joydev K. Laha,
• Pankaj Gupta and
• Amitava Hazra

Beilstein J. Org. Chem. 2023, 19, 771–777, doi:10.3762/bjoc.19.57

• their unique stability, defined reactivity, and versatility in organic synthesis [2]. Leveraging their electron-deficient nature, N-arylsulfonylimines are widely used in organic transformations including nucleophilic addition, cycloaddition, imino-aldol reaction, ene reactions, aza-Friedel–Crafts

Construction of hexabenzocoronene-based chiral nanographenes

• Ranran Li,
• Di Wang,
• Shengtao Li and
• Peng An

Beilstein J. Org. Chem. 2023, 19, 736–751, doi:10.3762/bjoc.19.54

• helical NG 44 containing [6]helicene structure and an azulene unit (Scheme 5). Through a two-fold Diels–Alder cycloaddition from 1,4-bis(2-ethynylphenyl)buta-1,3-diyne (41) and tetracyclone 11, alkyne 42 was obtained in an 83% yield. Then unique diiodide precursor 43 was obtained by ICl-mediated

• –Alder cycloaddition to afford compound 45 in a 79% yield. Due to the steric hindrance from two bulky tert-butyl groups on the benzene rings in the adjacent hexaphenylbenzene monomers in precursor 45, two [5]helicenes were formed in the oxidative cyclodehydrognation reaction, which gave compound 46 as

• Sonogashira cross-coupling reaction of phenylacetylene 50 and 1,4-dibromotetrafluorobenzene. The resulting bis[aryl(ethynyl)]tetrafluorobenzene 59 was able to undergo a 2-fold [4 + 2] cycloaddition reaction with cyclopentadienone 2, affording polyaromatic 60 in a 70% yield. The final step was the Scholl

Strategies in the synthesis of dibenzo[b,f]heteropines

• David I. H. Maier,
• Barend C. B. Bezuidenhoudt and
• Charlene Marais

Beilstein J. Org. Chem. 2023, 19, 700–718, doi:10.3762/bjoc.19.51

• ) chloride (Scheme 26). Alkyne–carbonyl metathesis is proposed to proceed via [2 + 2] cycloaddition and –reversion steps, catalysed by a Brønsted or Lewis acid, with the catalyst proposed to form a σ-complex with the carbonyl group and/or a π-complex with the alkyne [68]. 3.7 Hydroarylation The construction

Nucleophile-induced ring contraction in pyrrolo[2,1-c][1,4]benzothiazines: access to pyrrolo[2,1-b][1,3]benzothiazoles

• Ekaterina A. Lystsova,
• Maksim V. Dmitriev,
• Andrey N. Maslivets and
• Ekaterina E. Khramtsova

Beilstein J. Org. Chem. 2023, 19, 646–657, doi:10.3762/bjoc.19.46

• -benzothiazol-2-yl(diazo)acetates (Scheme 1, entry 3) [12], dearomative [3 + 2] cycloaddition reactions of benzothiazoles with cyclopropanes (Scheme 1, entry 4) [13][14][15], multicomponent reactions (MCRs) of benzothiazoles, isocyanides and 2-methylidenemalonates (Scheme 1, entry 5) [16], 1,3-dipolar

Access to cyclopropanes with geminal trifluoromethyl and difluoromethylphosphonate groups

• Ita Hajdin,
• Romana Pajkert,
• Mira Keßler,
• Jianlin Han,
• Haibo Mei and
• Gerd-Volker Röschenthaler

Beilstein J. Org. Chem. 2023, 19, 541–549, doi:10.3762/bjoc.19.39

• target diazo reagent 5, which contains both a trifluoromethyl and a difluoromethylphosphonate moiety, was isolated as a stable, non-volatile liquid (Scheme 2). To highlight the synthetic utility of the novel carbene precursor 5, subsequent [2 + 1] cycloaddition reactions with selected terminal aromatic

• diastereoisomer adopts trans configuration (Figure 1). Furthermore, terminal aliphatic alkenes as well as N-Boc-allylamine were subjected to [2 + 1] cycloaddition reactions with the carbene precursor 5. The results are summarized in Scheme 4. As observed, the procedure was successful with a series of terminal

Computational studies of Brønsted acid-catalyzed transannular cycloadditions of cycloalkenone hydrazones

• Manuel Pedrón,
• Jana Sendra,
• Irene Ginés,
• Tomás Tejero,
• Jose L. Vicario and
• Pedro Merino

Beilstein J. Org. Chem. 2023, 19, 477–486, doi:10.3762/bjoc.19.37

• studied by using DFT. The Houk's distortion model has been employed to evaluate the influence of the tether in the cycloaddition reaction. That model has been extended to determine the contribution of each tether and, more importantly, the effect exerted between them. In addition to the distortion induced

• ; Introduction Transannular cycloaddition reactions (TCRs) are useful for the synthesis of complex natural products and other biologically active compounds with high efficiency and stereoselectivity [1][2][3][4]. There are several different ways in which TCRs can occur, depending on the nature of the starting

• and co-workers demonstrated for transannular Diels–Alder cycloaddition reactions of symmetrically tethered large systems (10–18-membered rings) [29]. In this context, we have recently reported the transannular enantioselective (3 + 2) cycloaddition of cycloalkenone hydrazones under Brønsted acid

CuAAC-inspired synthesis of 1,2,3-triazole-bridged porphyrin conjugates: an overview

• Dileep Kumar Singh

Beilstein J. Org. Chem. 2023, 19, 349–379, doi:10.3762/bjoc.19.29

• -dipolar cycloaddition reaction between an azide and a terminal alkyne, also popular as "click reaction" or CuAAC reaction. Moreover, the 1,2,3-triazole ring also serves as a spacer and an electron transfer bridge between the porphyrin and the attached chromophores. In order to provide a critical overview

• of the synthesis and properties of various porphyrin-triazole hybrids, this review will discuss some of the key reactions involved in the preparation of triazole-linked porphyrin conjugates. Keywords: azide–alkyne; click chemistry; CuAAC; 1,3-dipolar cycloaddition; porphyrin; 1,2,3-triazole

• connect a porphyrin with a chromophoric group. Among these, the copper(I)-catalyzed Huisgen 1,3-dipolar cycloaddition reaction [1][2] of azides with terminal alkynes is a popular and well established process to link a porphyrin with other moieties via 1,2,3-triazole group [3] (Figure 1). The term “click

Strategies to access the [5-8] bicyclic core encountered in the sesquiterpene, diterpene and sesterterpene series

• Cécile Alleman,
• Charlène Gadais,
• Laurent Legentil and
• François-Hugues Porée

Beilstein J. Org. Chem. 2023, 19, 245–281, doi:10.3762/bjoc.19.23

• construction of the 8-membered ring from an appropriate cyclopentane precursor. The proposed strategies include metathesis, Nozaki–Hiyama–Kishi (NHK) cyclization, Pd-mediated cyclization, radical cyclization, Pauson–Khand reaction, Lewis acid-promoted cyclization, rearrangement, cycloaddition and biocatalysis

• precursor. The proposed strategies include metathesis, Nozaki–Hiyama–Kishi (NHK) cyclization, Pd-mediated cyclization, radical cyclization (including SmI2), Pauson–Khand reaction, Lewis acid-promoted cyclization, rearrangement, cycloaddition, and biocatalysis. In particular, the purpose will focus on the

• exo Diels–Alder cycloaddition, which resulted in compound 159. The enol ether was oxidized by ceric ammonium nitrate (CAN) to deliver intermediate 160, which was further subjected to an iron-catalyzed hydrogen atom transfer generating tricyclic intermediate 161. Further functionalization permitted the

Germacrene B – a central intermediate in sesquiterpene biosynthesis

• Houchao Xu and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2023, 19, 186–203, doi:10.3762/bjoc.19.18

• acetone and water to a hemiacetal that can decompose to 11 (Scheme 4B) [43]. Furthermore, 1 shows an interesting photochemistry (Scheme 4C). A [2 + 2] cycloaddition of the endocyclic double bonds yields 12 whose formation is understandable from conformers 1c and 1d. The all-cis stereoisomer 14 requires a

• photochemical E/Z isomerisation to 13 prior to [2 + 2] cycloaddition. Further photochemical products from 1 include 5, 15 that may be formed through a biradical mechanism, and rearranged 16 [51]. Germacrene B (1) has planar chirality (Scheme 4D), but recovery of the starting material from an incomplete

1,4-Dithianes: attractive C2-building blocks for the synthesis of complex molecular architectures

• Bram Ryckaert,
• Ellen Demeyere,
• Frederick Degroote,
• Hilde Janssens and
• Johan M. Winne

Beilstein J. Org. Chem. 2023, 19, 115–132, doi:10.3762/bjoc.19.12

• reverse (3 + 2) cycloaddition which expels a heteroatomic anion via a β-elimination-type mechanism somewhat similar to a classical Grob-type fragmentation. Similarly, 1,3-dithiolanes undergo fragmentation at relatively low reaction temperatures, limiting their synthetic application to alkylation with

• -tetroxide ring gives the cyclohexa-1,4-diene intermediate 39. This intermediate can then be easily oxidized to afford the aromatic adduct 40, which is the known cycloaddition product of furan and benzyne. Although this synthetic equivalent of benzyne requires a lengthy work-around, all synthetic operations

• single-cis conformation. Ando and co-workers prepared the symmetrical 1,4-dithiane 41 (Scheme 9a) [55], and amply illustrated the concept by reacting it in a [4 + 2] cycloaddition with a highly reactive diazo dienophile (Cookson’s reagent or 4-phenyl-1,2,4-triazoline-3,5-dione (PTAD)) to afford the bis

Practical synthesis of isocoumarins via Rh(III)-catalyzed C–H activation/annulation cascade

• Qian-Ci Gao,
• Yi-Fei Li,
• Jun Xuan and
• Xiao-Qiang Hu

Beilstein J. Org. Chem. 2023, 19, 100–106, doi:10.3762/bjoc.19.10

• recently, the same group developed an efficient Rh(III)-catalyzed C–H cross-coupling of enaminones with diazodicarbonyls for the divergent construction of isocoumarins and naphthalenes [27]. Moreover, Loh et al. disclosed a Rh-catalyzed formal [4 + 2] cycloaddition of enaminones with diazocarbonyls [28

Organophosphorus chemistry: from model to application

• György Keglevich

Beilstein J. Org. Chem. 2023, 19, 89–90, doi:10.3762/bjoc.19.8

• chemistry and beyond. Quantum chemical calculations are a great support for organic chemists when exploring structures, reactivities, and mechanisms. In this thematic issue, the Diels–Alder cycloaddition of 2-phosphaindolizine, 1-aza-2-phosphaindolizine, 3-aza-2-phosphaindolizine, and 1,3-diaza-2

Catalytic aza-Nazarov cyclization reactions to access α-methylene-γ-lactam heterocycles

• Bilge Banu Yagci,
• Selin Ezgi Donmez,
• Onur Şahin and
• Yunus Emre Türkmen

Beilstein J. Org. Chem. 2023, 19, 66–77, doi:10.3762/bjoc.19.6

• on the success of the catalytic aza-Nazarov reaction. Keywords: α-methylene-γ-lactam; aza-Nazarov reaction; β-silicon effect; heterocycles; intramolecular cyclization; Introduction The rapid construction of aliphatic heterocycles from acyclic building blocks via cyclization or cycloaddition

Combining the best of both worlds: radical-based divergent total synthesis

• Kyriaki Gennaiou,
• Antonios Kelesidis,
• Maria Kourgiantaki and
• Alexandros L. Zografos

Beilstein J. Org. Chem. 2023, 19, 1–26, doi:10.3762/bjoc.19.1

• pyrone meroterpenoids on sclareolide (29). Key reaction of this strategy was the formal [3 + 3] cycloaddition, catalyzed by phosphoric acid 33, followed by addition of a pyrone residue 32 to sclareolide-derived aldehyde 31, which served as the common synthetic intermediate for the synthesis (Scheme 3

• commenced with the generation of 107 from cyclopentenone 105 and aryl aldehyde 106 in a three-step sequence. An oxidative dearomatization induced a [5 + 2] cycloaddition–pinacol rearrangement of 107 to 109, according to previous studies of the same group (Scheme 9) [59][60][61]. The key HAT-mediated

Inline purification in continuous flow synthesis – opportunities and challenges

• Jorge García-Lacuna and
• Marcus Baumann

Beilstein J. Org. Chem. 2022, 18, 1720–1740, doi:10.3762/bjoc.18.182

• -butylimino-2-diethylamino-1,3-dimethylperhydro-1,3,2-diazaphosphorine on polystyrene) which is valuable for reaction scale-ups [75] is used. Alternatively, a CuAAc (copper-catalyzed azide–alkyne cycloaddition) reaction has been demonstrated where the copper catalyst is supported on an Amberlist A-21 resin

Total synthesis of grayanane natural products

• Nicolas Fay,
• Rémi Blieck,
• Cyrille Kouklovsky and
• Aurélien de la Torre

Beilstein J. Org. Chem. 2022, 18, 1707–1719, doi:10.3762/bjoc.18.181

• , protection of the secondary alcohol as a benzyl ether, oxidation of the sulfur and Pummerer rearrangement (Scheme 3). A Wittig reaction gave compounds 8, as a 10:1 separable diastereomeric mixture. A diastereoselective Diels–Alder cycloaddition followed by oxidation of the resulting epimeric mixture gave

• Diels–Alder cycloaddition. Treatment of 38 with TBAF followed by PhI(OAc)2 led to the formation of 39, having the A and B ring correctly arranged. The product was obtained in 70% yield, along with 25% of an undesired diastereoisomer. The dimethoxy functionality was reduced in the presence of Kagan’s

• by diastereoselective cycloaddition followed by C15–C16 epoxidation with m-CPBA. Reductive cleavage of the O–O bond by Zn/AcOH treatment afforded epoxide 53 as a single diastereomer in two steps and 65% yield. The correct bicyclo[3.2.1]octane was obtained by Wagner–Meerwein epoxide rearrangement

Redox-active molecules as organocatalysts for selective oxidative transformations – an unperceived organocatalysis field

• Elena R. Lopat’eva,
• Igor B. Krylov,
• Dmitry A. Lapshin and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2022, 18, 1672–1695, doi:10.3762/bjoc.18.179

• , such as aldol reactions, Michael reactions, cycloaddition reactions, etc. Organophotoredox catalysis has emerged recently as another important catalysis type which has gained much attention and has been quite well-reviewed. At the same time, there are a significant number of other processes, especially

A novel bis-triazole scaffold accessed via two tandem [3 + 2] cycloaddition events including an uncatalyzed, room temperature azide–alkyne click reaction

• Ksenia Malkova,
• Andrey Bubyrev,
• Vasilisa Krivovicheva,
• Dmitry Dar’in,
• Alexander Bunev and
• Mikhail Krasavin

Beilstein J. Org. Chem. 2022, 18, 1636–1641, doi:10.3762/bjoc.18.175

• molecular scaffold. Pondering various opportunities for post-condensational modifications of the 1,5-disubstituted 1,2,3-triazole core according to this strategy, we turned our attention to such powerful transformation as the azide–alkyne [3 + 2] cycloaddition (also known as the azide–alkyne click reaction

• ) [6]. Indeed, if an alkyne and an azido group were strategically positioned within the structure of the amine and the aldehyde components for the reaction with 1, subsequent intramolecular azide–alkyne cycloaddition would be a feasible event which would create a polycyclic bis-1,2,3-triazole framework

• (Figure 1). Herein, we report on a successful realization of this strategy. Results and Discussion To test the possibility of a tandem double cycloaddition reaction between 1, an alkyne-containing amine and an azide-containing aldehyde, we set up a reaction of 1 with o-azidobenzaldehyde (3a) and

One-pot double annulations to confer diastereoselective spirooxindolepyrrolothiazoles

• Juan Lu,
• Bin Yao,
• Desheng Zhan,
• Zhuo Sun,
• Yun Ji and
• Xiaofeng Zhang

Beilstein J. Org. Chem. 2022, 18, 1607–1616, doi:10.3762/bjoc.18.171

• 10.3762/bjoc.18.171 Abstract A novel four-component reaction in one pot as an atom- and step-economic process was developed to synthesize diastereoselectively spirooxindolepyrrolothiazoles through sequential N,S-acetalation of aldehydes with cysteine and decarboxylative [3 + 2] cycloaddition with olefinic

• introduced in this study. Subsequently one equivalent of aldehyde and olefinic oxindole in situ were followed by decarboxylative 1,3-dipolar cycloaddition for diastereoselective synthesis of spirooxindolepyrrolothiazoles with generating 5 new bonds, 5 stereocenters and two heterocycles (Scheme 1C and Scheme

•  2C). Results and Discussion The optimized reaction conditions of stepwise, one-pot and cascade (two-step with one operational step) processes for N,S-acetalation and decarboxylative 1,3-dipolar cycloaddition were developed by using two equivalents of 4-bromobenzaldehyde (1a), ʟ-cysteine (2) and

Functionalization of imidazole N-oxide: a recent discovery in organic transformations

• Koustav Singha,
• Imran Habib and
• Mossaraf Hossain

Beilstein J. Org. Chem. 2022, 18, 1575–1588, doi:10.3762/bjoc.18.168

• , like cycloaddition, metal-free coupling reactions, three-component or multicomponent reactions etc., which use N-oxide chemistry. In 2021 Timofey D. Moseev and co-workers unfolded an attractive procedure of the coupling reaction between 2H-imidazole 1-oxides and polyphenols under metal-free conditions

• the past years are discussed. This review contains cycloaddition reactions, nucleophilic halogenation reactions, metal-free coupling reactions, formation of N-heterocyclic carbenes, and multicomponent reactions, mainly three-component reactions. The mentioned methodologies have been performed by

• more research using imidazole N-oxides as precursors to make this research field flourishing in near future. Review Cycloaddition reactions In 2020, Anton V. Kutasevich et al. unfolded a very interesting deoxygenative reaction procedure where 2-unsubstituted imidazole N-oxides reacted with ethyl

A facile approach to spiro[dihydrofuran-2,3'-oxindoles] via formal [4 + 1] annulation reaction of fused 1H-pyrrole-2,3-diones with diazooxindoles

• Pavel A. Topanov,
• Anna A. Maslivets,
• Maksim V. Dmitriev,
• Irina V. Mashevskaya,
• Yurii V. Shklyaev and
• Andrey N. Maslivets

Beilstein J. Org. Chem. 2022, 18, 1532–1538, doi:10.3762/bjoc.18.162

• , Perm 614990, Russian Federation 10.3762/bjoc.18.162 Abstract There has been developed an easy synthetic approach to spiro[dihydrofuran-2,3'-oxindoles] via a highly diastereoselective formal [4 + 1] cycloaddition reaction of [e]-fused 1H-pyrrole-2,3-diones with diazooxindoles. The described novel

• and J [16] were also isolated from the fungus Penicillium commune and contain a furan fragment spiro-annulated by 2-oxindole. These compounds exhibit anticancer [13] and antimicrobial [17] activities. One of the expeditious methods for obtaining dihydrofurans is the cycloaddition reaction of diazo

• compounds to molecules containing an enone fragment. Cycloaddition reactions involving diazo and enone moieties are usually carried out using transition-metal catalysis [18][19][20], with catalyst-free reactions being carried out only with the participation of reactive unsubstituted diazomethane [21][22][23

New triazole-substituted triterpene derivatives exhibiting anti-RSV activity: synthesis, biological evaluation, and molecular modeling

• Elenilson F. da Silva,
• Krist Helen Antunes Fernandes,
• Denise Diedrich,
• Jessica Gotardi,
• Marcia Silvana Freire Franco,
• Carlos Henrique Tomich de Paula da Silva,
• Ana Paula Duarte de Souza and
• Simone Cristina Baggio Gnoatto

Beilstein J. Org. Chem. 2022, 18, 1524–1531, doi:10.3762/bjoc.18.161

• triterpenes to synthesize 1,2,3-triazole derivatives via the Huisgen 1,3-cycloaddition reaction, but, as far as we know, this is the first report of the application of click chemistry to triterpenes with this objective [35][36][37]. Click chemistry is one of the most important tools used for the synthesis of

Preparation of an advanced intermediate for the synthesis of leustroducsins and phoslactomycins by heterocycloaddition

• Anaïs Rousseau,
• Guillaume Vincent and
• Cyrille Kouklovsky

Beilstein J. Org. Chem. 2022, 18, 1385–1395, doi:10.3762/bjoc.18.143

• fragment was accomplished in a stereoselective fashion through a vinyllithium intermediate. An advanced synthetic intermediate was then obtained after functional group transformation. Keywords: cycloaddition; organolithium; stereoselective; total synthesis; Introduction Leustroducsins 1a–c and

• –O bond from an 1,2-oxazine, itself obtained by a nitroso Diels–Alder reaction from a chiral nitroso derivative and a functionalized diene (Figure 3). The nitroso Diels–Alder cycloaddition reaction has been well studied and has been used as a powerful tool for synthesis [19][20][21][22]. We have

• advantages over the related enol silyl ethers [24][25]: they are more stable towards acidic conditions, their electronic character contributes to high regioselectivity in cycloaddition reactions, and they can be converted to many other functions, including their hydrolysis to ketones [26]. In the other hand

Vicinal ketoesters – key intermediates in the total synthesis of natural products

• Marc Paul Beller and
• Ulrich Koert

Beilstein J. Org. Chem. 2022, 18, 1236–1248, doi:10.3762/bjoc.18.129

• of L. Overman et al. in 1997 [18] towards the originally proposed structure of palau’amine (44), a [3 + 2]-dipolar cycloaddition of α-ketoester 41 and the thiosemicarbazide 42-derived azomethine imine VI to the triazacyclopenta[cd]pentalene 43 was utilized as a key step (Scheme 7) [18][19][20][21

• cycloaddition delivered the advanced intermediate 43 in an efficient and elegant way. Jatropha-5,12-diene Towards the total synthesis of natural and unnatural jatrophane diterpenes, Hiersemann et al. used a highly efficient, intramolecular carbonyl-ene reaction of α-ketoester 49 (Scheme 8) [22]. The ketoester

• of an α-ketoester through Riley oxidation and its use in an α-ketol rearrangement in the synthesis of (−)-jiadifenoxolane A (36) [15]. Azomethine imine cycloaddition towards the synthesis of the proposed structure of palau’amine (44) [19]. Intramolecular diastereoselective carbonyl-ene reaction of an